Safety of Urate Elevation in Parkinson's Disease (SURE-PD)

• ClinicalTrials.gov Identifier: NCT00833690
• Recruitment Status: Completed
• First Posted: February 2, 2009
• Results First Posted: June 5, 2014
• Last Update Posted: June 5, 2014
• Sponsor: The Parkinson Study Group
• Collaborators: Massachusetts General Hospital; Harvard School of Public Health (HSPH); University of Rochester; Michael J. Fox Foundation for Parkinson's Research
• Information provided by (Responsible Party): Michael Schwarzschild, The Parkinson Study Group

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Parkinson Disease
• Interventions: Drug: Placebo; Drug: inosine
• Enrollment: 75

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Period Title: Overall Study
Started	25	24	26
Completed	21	22	26
Not Completed	4	2	0
Reason Not Completed
Withdrawal by Subject	1	0	0
Discontinued study drug	3	2	0

Baseline Characteristics

Arm/Group Title		[A:]Placebo	[B:]Mild	[C.]Moderate	Total
Arm/Group Description		Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation	Total of all reporting groups
Overall Number of Baseline Participants		25	24	26	75
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		61 (11)	62 (10)	62 (11)	62 (10)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
	Female	13 52.0%	14 58.3%	14 53.8%	41 54.7%
	Male	12 48.0%	10 41.7%	12 46.2%	34 45.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
	Hispanic or Latino	0 0.0%	2 8.3%	0 0.0%	2 2.7%
	Not Hispanic or Latino	25 100.0%	22 91.7%	26 100.0%	73 97.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	1 3.8%	1 1.3%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	24 96.0%	22 91.7%	24 92.3%	70 93.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 4.0%	2 8.3%	1 3.8%	4 5.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		25	24	26	75
Years since symptom onset; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		2.4 (1.3)	2.8 (1.9)	2.2 (2.0)	2.4 (1.8)
Years since diagnosis; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		1.1 (1.3)	1.3 (1.0)	0.6 (0.7)	1.0 (1.1)
Serum Urate; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		4.5 (0.7)	4.3 (1.2)	4.6 (0.9)	4.5 (0.9)
Serum urate in women; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		4.4 (0.8)	3.9 (1.3)	4.4 (0.8)	4.2 (1.0)
Serum urate in men; Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		4.7 (0.5)	5.0 (0.8)	4.9 (0.9)	4.8 (0.7)
United Parkinson's Disease Rating Scale (UPDRS) score total [1]; Mean (Standard Deviation); Unit of measure: Points
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		23 (10)	20 (9)	21 (10)	22 (10)
		[1] Measure Description: The UPDRS is designed to monitor disability and impairment due to Parkinson's disease. It comprises several parts. Part I evaluates "Mentation, Behavior, and Mood" (with a maximum of 16 points; more points are worse); Part II evaluates "Activities of Daily Living" (with a maximum of 52 points); Part III entails a "Motor Examination" (with a maximum of 108 points). Total score of Parts I-III sums the points from all parts and thus can range from a minimum of 0 (best) to a maximum of 176 (worst).
Montreal Cognitive Assessment (MoCA) [1]; Mean (Standard Deviation); Unit of measure: Score
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		28 (1.9)	28 (1.8)	28 (2.0)	28 (1.9)
		[1] Measure Description: The MoCA assesses short term and working memory, visual-spatial abilities, executive function, attention, concentration, language and orientation. The total score ranges from 0 to 30 (highest function).
Geriatric Depression Scale-short form (GDS-S) [1]; Mean (Standard Deviation); Unit of measure: Score
	Number Analyzed	25 participants	24 participants	26 participants	75 participants
		1.5 (1.9)	1.4 (1.7)	1.8 (2.6)	1.5 (2.1)
		[1] Measure Description: GDS-S is a short 15 'yes/no' question instrument for assessing depression in older adults. Questions are answered by the research participant (i.e., self-rater). Scores range range from 0 to 15 and higher scores represent greater depression. Scores of 5-9 and >9 have been correlated with mild and moderate-severe depression, respectively.

Outcome Measures

1. Primary Outcome

Title	Tolerability
Description	Defined as the extent to which assigned treatment could continue without prolonged dose reduction (>48 consecutive days or >73 cumulative days, which is 10% of total 2-year follow-up) due to adverse experiences (AEs), and was assessed after 6 and 24 months on study drug. Units of measure are percentage points (i.e., % of participants in the group).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	24	26
Measure Type: Number; Unit of Measure: percentage of participants
	96	96	100

2. Primary Outcome

Title	Tolerability
Description	Defined as the extent to which assigned treatment could continue without prolonged dose reduction (>48 consecutive days or >73 cumulative days, which is 10% of total 2-year follow-up) due to AEs, and was assessed after 6 and 24 months on study drug. Units of measure are percentage points (i.e., % of participants in the group).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	24	26
Measure Type: Number; Unit of Measure: percentage of participants
	86	92	96

3. Primary Outcome

Title	Safety
Description	Defined as absence of serious adverse experiences (SAEs) that warranted terminating an inosine treatment arm or the trial, as determined by the Data and Safety Monitoring Committee.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	24	26
Measure Type: Number; Unit of Measure: Events
	11	2	4

4. Secondary Outcome

Title	CSF Urate (All Patients)
Description	Urate concentration in cerebrospinal fluid (CSF)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	11	15	18
Mean (Standard Deviation); Unit of Measure: mcg/dL
	427 (190)	544 (148)	594 (175)

5. Secondary Outcome

Title	CSF Urate (Females)
Description	[Not Specified]
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	5	9	10
Mean (Standard Deviation); Unit of Measure: mcg/dL
	285 (69)	517 (169)	575 (176)

6. Secondary Outcome

Title	CSF Urate (Males)
Description	[Not Specified]
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	6	6	8
Mean (Standard Deviation); Unit of Measure: mcg/dL
	546 (178)	586 (113)	619 (184)

7. Secondary Outcome

Title	CSF Urate as a Proportion of Baseline Serum Urate (All Patients)
Description	Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	11	15	18
Mean (Standard Deviation); Unit of Measure: percentage of baseline serum urate
	9.6 (4.0)	13.1 (4.0)	13.4 (4.3)

8. Secondary Outcome

Title	CSF Urate as a Proportion of Baseline Serum Urate (Females)
Description	Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	5	9	10
Mean (Standard Deviation); Unit of Measure: percentage of baseline serum urate
	6.7 (1.8)	13.5 (5.0)	13.3 (5.0)

9. Secondary Outcome

Title	CSF Urate as a Proportion of Baseline Serum Urate (Males)
Description	Although CSF urate was not measured at baseline, the change of CSF urate from baseline may be indirectly estimated by the ratio of CSF urate (at the 12 week visit when a lumbar puncture was performed) to the serum urate measured in the same subject at baseline. Baseline serum urate and CSF urate concentrations are directly correlated with one another (i.e., individuals with higher serum urate concentrations tend to have higher CSF urate concentrations) even though the concentration of urate in CSF is typically ~10% of that in serum. The ratio of CSF urate to baseline serum urate can be expressed as the percentage of the value of urate concentration measured in serum at baseline that is measured in CSF (at week 12).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	6	6	8
Mean (Standard Deviation); Unit of Measure: percentage of baseline serum urate
	12.0 (3.8)	12.4 (2.2)	13.4 (3.5)

10. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn prior to enrollment
Time Frame	Screening Visits, up to 45 days prior to Baseline Visit. Specifically, Screening Visit 1 occurred between day -45 and -4; Screening Visit 2 occurred between day -43 and -2.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
Screening Visit 1	4.63 (0.62)	4.28 (0.86)	4.39 (0.78)
Screening Visit 2	4.78 (0.6)	4.4 (0.88)	4.48 (0.75)

11. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn prior to enrollment
Time Frame	Baseline Visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	23	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.54 (0.69)	4.32 (1.2)	4.62 (0.86)

12. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 01 (Week 2; 14 +/- 3 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.8 (0.65)	6.44 (1.29)	6.93 (1.42)

13. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 02 (Week 4; 28 +/- 3 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.73 (0.65)	6.58 (0.87)	7.9 (1.29)

14. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 03 (Week 6; 42 +/- 3 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.85 (0.77)	6.69 (0.78)	7.51 (1.24)

15. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 04 (Week 9; 63 +/- 5 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.62 (0.58)	6.81 (1.22)	7.62 (1.02)

16. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn before taking study drug that day
Time Frame	Visit 05 (Week 12; 84 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.74 (0.59)	5.85 (1.02)	6.91 (1.09)

17. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 06 (Month 6; 180 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	23	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.85 (1)	6.94 (1.6)	8.27 (0.74)

18. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 07 (Month 9; 270 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.77 (0.89)	6.77 (1.51)	8.06 (1.2)

19. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 08 (Month 12; 360 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	22	23	24
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.79 (0.89)	6.87 (1.05)	7.41 (0.96)

20. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 09 (Month 15; 450 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	18	19	22
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.62 (0.69)	7.26 (0.96)	7.64 (1.2)

21. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 10 (Month 18; 540 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	16	16	17
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.58 (0.76)	7 (0.97)	7.64 (0.98)

22. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 11 (Month 21; 630 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	7	11	14
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.6 (0.47)	7.12 (1.21)	7.56 (1.08)

23. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	Visit 12 (Month 24; 720 +/- 7 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	5	10	9
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.41 (0.99)	6.84 (0.76)	7.19 (1.19)

24. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn after taking study drug that day
Time Frame	End of Study Drug Visit (ESD) (Month 9-24; 263-727 days after Baseline Visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.66 (0.79)	6.48 (1.25)	7.55 (1.6)

25. Secondary Outcome

Title	Serum Urate
Description	From blood sample drawn a month after stopping study drug
Time Frame	Safety Visit (SV); 30 +/- 3 days following ESD or Month 24 Visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	23	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	4.74 (0.77)	4.69 (1.28)	4.38 (0.78)

26. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 01 from Baseline (i.e., between -45 days and +2 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	25	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.15 (0.41)	2.1 (0.83)	2.44 (1.07)

27. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 02 from Baseline (i.e., between -45 days and +4 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.09 (0.48)	2.24 (1.13)	3.41 (1.22)

28. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 03 from Baseline (i.e., between -45 days and +6 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.22 (0.51)	2.35 (1.03)	3.02 (1.13)

29. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 04 from Baseline (i.e., between -45 days and +9 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	-0.02 (0.35)	2.47 (1.34)	3.13 (1.16)

30. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 05 from Baseline (i.e., between -45 days and +12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.1 (0.42)	1.51 (0.8)	2.42 (1.08)

31. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 06 from Baseline (i.e., between -45 days and +6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	23	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.21 (0.86)	2.55 (1.4)	3.78 (0.95)

32. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 07 from Baseline (i.e., between -45 days and +9 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	24	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.14 (0.68)	2.43 (1.56)	3.56 (1.51)

33. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 08 from Baseline (i.e., between -45 days and +12 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	22	23	24
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.2 (0.78)	2.46 (1.24)	2.96 (1.28)

34. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 09 from Baseline (i.e., between -45 days and +15 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	18	19	22
Mean (Standard Deviation); Unit of Measure: mg/dL
	0 (0.67)	2.9 (0.98)	3.19 (1.18)

35. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 10 from Baseline (i.e., between -45 days and +18 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	16	16	17
Mean (Standard Deviation); Unit of Measure: mg/dL
	-0.07 (0.43)	2.49 (1.07)	3.26 (1.25)

36. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 11 from Baseline (i.e., between -45 days and +21 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	7	11	14
Mean (Standard Deviation); Unit of Measure: mg/dL
	-0.07 (0.59)	2.53 (1.12)	3.11 (1.46)

37. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Visit 12 from Baseline (i.e., between -45 days and +24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	5	10	9
Mean (Standard Deviation); Unit of Measure: mg/dL
	-0.29 (1.08)	2.22 (0.96)	2.93 (1.38)

38. Secondary Outcome

Title	Change in Serum Urate
Description	Change from an Average of Baseline and Screening Visits
Time Frame	Safety Visit (SV) from Baseline (i.e., between -45 days and +760 days [+1 month after ESD Visit])

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	24	23	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.1 (0.62)	0.35 (0.88)	-0.11 (0.61)

39. Secondary Outcome

Title	Change in Serum Urate
Description	Change from Last Visit on Study Drug
Time Frame	Safety Visit (SV) from End of Study Drug Visit (ESD); i.e., between +263 and +760 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[A:]Placebo	[B:]Mild	[C.]Moderate
Arm/Group Description:	Placebo to produce no urate elevation	Inosine to produce a mild urate elevation	Inosine to produce a moderate urate elevation
Overall Number of Participants Analyzed	23	23	26
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.12 (0.51)	-1.8 (1.33)	-3.2 (1.63)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	[A:]Placebo		[B:]Mild		[C.]Moderate
Arm/Group Description	Placebo to produce no urate elevation		Inosine to produce a mild urate elevation		Inosine to produce a moderate urate elevation
All-Cause Mortality
	[A:]Placebo		[B:]Mild		[C.]Moderate
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	[A:]Placebo		[B:]Mild		[C.]Moderate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36.00%)		2/24 (8.33%)		4/26 (15.38%)
Cardiac disorders
Acute coronary syndrome † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Coronary artery disease † 1	0/25 (0.00%)	0	0/24 (0.00%)	0	1/26 (3.85%)	1
Hepatobiliary disorders
Cholecystitis † 1	0/25 (0.00%)	0	0/24 (0.00%)	0	1/26 (3.85%)	1
Infections and infestations
Human ehrlichiosis † 1	0/25 (0.00%)	0	1/24 (4.17%)	1	0/26 (0.00%)	0
Pneumonia † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Urosepsis † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Injury, poisoning and procedural complications
Cervical vertebral fracture † 1	0/25 (0.00%)	0	1/24 (4.17%)	1	0/26 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthritis † 1	3/25 (12.00%)	3	0/24 (0.00%)	0	0/26 (0.00%)	0
Synovial cyst † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Nervous system disorders
Cerebrovascular accident † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Radiculopathy † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Psychiatric disorders
Depression † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
Suicidal ideation † 1	0/25 (0.00%)	0	0/24 (0.00%)	0	1/26 (3.85%)	1
Renal and urinary disorders
Nephrolithiasis † 1	0/25 (0.00%)	0	0/24 (0.00%)	0	1/26 (3.85%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	0/26 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	[A:]Placebo		[B:]Mild		[C.]Moderate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/25 (72.00%)		22/24 (91.67%)		20/26 (76.92%)
Gastrointestinal disorders
Constipation † 1	3/25 (12.00%)	3	0/24 (0.00%)	0	0/26 (0.00%)	0
Dry Mouth † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	3/26 (11.54%)	3
Dyspepsia † 1	1/25 (4.00%)	1	2/24 (8.33%)	2	1/26 (3.85%)	1
General disorders
Fatigue † 1	1/25 (4.00%)	1	1/24 (4.17%)	1	4/26 (15.38%)	4
Oedema peripheral † 1	0/25 (0.00%)	0	2/24 (8.33%)	3	1/26 (3.85%)	1
Infections and infestations
Sinusitis † 1	3/25 (12.00%)	3	0/24 (0.00%)	0	0/26 (0.00%)	0
Upper respiratory track infection † 1	2/25 (8.00%)	2	1/24 (4.17%)	1	0/26 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	0/25 (0.00%)	0	2/24 (8.33%)	2	1/26 (3.85%)	1
Metabolism and nutrition disorders
Dehydration † 1	2/25 (8.00%)	2	0/24 (0.00%)	0	0/26 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/25 (8.00%)	3	3/24 (12.50%)	4	4/26 (15.38%)	4
Arthritis † 1	4/25 (16.00%)	4	0/24 (0.00%)	0	0/26 (0.00%)	0
Back pain † 1	3/25 (12.00%)	4	2/24 (8.33%)	2	4/26 (15.38%)	6
Muscle spasms † 1	0/25 (0.00%)	0	2/24 (8.33%)	2	0/26 (0.00%)	0
Musculoskeletal pain † 1	1/25 (4.00%)	1	3/24 (12.50%)	3	0/26 (0.00%)	0
Musculoskeletal stiffness † 1	0/25 (0.00%)	0	2/24 (8.33%)	2	0/26 (0.00%)	0
Pain in extremity † 1	1/25 (4.00%)	1	3/24 (12.50%)	4	2/26 (7.69%)	2
Nervous system disorders
Headache † 1	2/25 (8.00%)	2	1/24 (4.17%)	1	0/26 (0.00%)	0
Tremor † 1	0/25 (0.00%)	0	0/24 (0.00%)	0	2/26 (7.69%)	2
Psychiatric disorders
Anxiety † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	2/26 (7.69%)	2
Depression † 1	4/25 (16.00%)	4	1/24 (4.17%)	1	3/26 (11.54%)	3
Insomnia † 1	2/25 (8.00%)	2	2/24 (8.33%)	2	2/26 (7.69%)	2
Suicidal ideation † 1	1/25 (4.00%)	1	0/24 (0.00%)	0	2/26 (7.69%)	2
Renal and urinary disorders
Nephrolithiasis † 1	0/25 (0.00%)	0	1/24 (4.17%)	1	2/26 (7.69%)	2
Respiratory, thoracic and mediastinal disorders
Cough † 1	2/25 (8.00%)	3	0/24 (0.00%)	0	1/26 (3.85%)	1
Dyspnoea † 1	2/25 (8.00%)	2	0/24 (0.00%)	0	0/26 (0.00%)	0
Pharyngolaryngeal pain † 1	2/25 (8.00%)	2	0/24 (0.00%)	0	0/26 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	0/25 (0.00%)	0	0/24 (0.00%)	0	2/26 (7.69%)	2
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (11.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Michael A. Schwarzschild, MD, PhD
• Organization: The Parkinson Study Group
• Phone: 617-724-9611
• EMail: mschwarzschild@partners.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schwarzschild MA, Macklin EA, Bakshi R, Battacharyya S, Logan R, Espay AJ, Hung AY, Bwala G, Goetz CG, Russell DS, Goudreau JL, Parashos SA, Saint-Hilaire MH, Rudolph A, Hare JM, Curhan GC, Ascherio A; Parkinson Study Group SURE-PD Investigators. Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial. Neurology. 2019 Oct 1;93(14):e1328-e1338. doi: 10.1212/WNL.0000000000008194. Epub 2019 Sep 4.

Parkinson Study Group SURE-PD Investigators; Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, Oakes D, Rudolph A, Shoulson I, Tennis MK, Espay AJ, Gartner M, Hung A, Bwala G, Lenehan R, Encarnacion E, Ainslie M, Castillo R, Togasaki D, Barles G, Friedman JH, Niles L, Carter JH, Murray M, Goetz CG, Jaglin J, Ahmed A, Russell DS, Cotto C, Goudreau JL, Russell D, Parashos SA, Ede P, Saint-Hilaire MH, Thomas CA, James R, Stacy MA, Johnson J, Gauger L, Antonelle de Marcaida J, Thurlow S, Isaacson SH, Carvajal L, Rao J, Cook M, Hope-Porche C, McClurg L, Grasso DL, Logan R, Orme C, Ross T, Brocht AF, Constantinescu R, Sharma S, Venuto C, Weber J, Eaton K. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2014 Feb;71(2):141-50. doi: 10.1001/jamaneurol.2013.5528.

• Responsible Party: Michael Schwarzschild, The Parkinson Study Group
• ClinicalTrials.gov Identifier: NCT00833690
• Other Study ID Numbers: INO-PD-P2-2008
• First Submitted: January 27, 2009
• First Posted: February 2, 2009
• Results First Submitted: December 26, 2013
• Results First Posted: June 5, 2014
• Last Update Posted: June 5, 2014