Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00307164

First received: March 23, 2006

Last updated: November 25, 2013

Last verified: November 2013

History of Changes

Results First Received: August 23, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver); Primary Purpose: Treatment
Conditions:	HIV Infections Lipoatrophy
Interventions:	Drug: NucleomaxX Drug: NucleomaxX placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruited at AIDS Clinical Trials Units in the United States and Puerto Rico. Recruitment occurred between October 5, 2006 (date first subject was randomized) and January 7, 2008 (date last subject was randomized).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 167 subjects were randomized, and results are reported for 165 eligible participants; two subjects never started study medication and were excluded from all analyses. The subjects were stratified by antiretroviral therapy use, stavudine (d4T) or zidovudine (AZT/ZDV).

Reporting Groups

	Description
NucleomaxX	Participants received NucleomaxX for uridine through week 48
Placebo	Participants received NucleomaxX placebo through week 48

Participant Flow: Overall Study

	NucleomaxX	Placebo
STARTED	83	82
COMPLETED	68	68
NOT COMPLETED	15	14
Death	1	0
Severe debilitation, unable to continue	1	0
Subject/parent not able to get to clinic	2	1
Withdrawal by Subject	1	8
Not compliant with requirements	4	4
Lost to Follow-up	6	1

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
NucleomaxX	Participants received NucleomaxX for uridine through week 48
Placebo	Participants received NucleomaxX placebo through week 48
Total	Total of all reporting groups

Baseline Measures

	NucleomaxX	Placebo	Total
Number of Participants [units: participants]	83	82	165
Age [units: years] Mean (Standard Deviation)	48.4 (7.78)	48.4 (6.46)	48.4 (7.13)
Age, Customized [units: Participants]
30-39 Years	9	10	19
40-49 Years	38	32	70
50-59 Years	28	38	66
60-69 Years	8	2	10
Gender [units: participants]
Female	8	7	15
Male	75	75	150
Race/Ethnicity, Customized [units: Participants]
White Non-Hispanic	50	52	102
Black Non-Hispanic	11	14	25
Hispanic (Regardless of Race)	15	12	27
Asian, Pacific Islander	3	1	4
Native American, Alaskan Native	3	2	5
Other (More than One Race)	1	0	1
Unknown	0	1	1
Region of Enrollment [units: participants]
United States	81	81	162
Puerto Rico	2	1	3
Antiretroviral Therapy Used (Stratification) [units: Participants]
AZT-Containing	63	63	126
d4T-Containing	20	19	39
HIV-1 RNA (copies/mL) Category [units: Participants]
<=50 Copies	70	64	134
>50 Copies	13	18	31
CD4+ Count (NucleomaxX sample size (N)=80, Placebo N=80) [units: Cells/mm^3] Median (Inter-Quartile Range)	506 (353 to 724)	504 (376 to 710)	506 (359 to 714)
Limb fat [units: Grams] Median (Inter-Quartile Range)	3149 (1833 to 4210)	2995 (2082 to 4847)	3037 (2002 to 4403)
Trunk fat [units: Grams] Median (Inter-Quartile Range)	8175 (5784 to 10931)	7795 (5327 to 10825)	8114 (5397 to 10898)
Fasting lactate (NucleomaxX N=76, Placebo N=75) [units: mmol/L] Median (Inter-Quartile Range)	1.3 (1.0 to 1.7)	1.2 (0.9 to 1.5)	1.3 (0.9 to 1.6)
Fasting glucose (NucleomaxX N=82, Placebo N=82) [units: mg/dL] Median (Inter-Quartile Range)	90 (84 to 98)	87 (81 to 95)	89 (82 to 97)
Fasting total cholesterol (NucleomaxX N=82, Placebo N=81) [units: mg/dL] Median (Inter-Quartile Range)	194 (163 to 216)	190 (166 to 211)	193 (166 to 215)
Fasting high-density lipoprotein (HDL) (NucleomaxX N=82, Placebo N=80) [units: mg/dL] Median (Inter-Quartile Range)	39 (33 to 49)	37 (31 to 47)	38 (32 to 49)
Fasting non-high-density lipoprotein (non-HDL) (NucleomaxX N=77, Placebo N=69) [units: mg/dL] Median (Inter-Quartile Range)	139 (123 to 168)	145 (115 to 166)	143 (121 to 167)
Fasting low-density lipoprotein (LDL) (NucleomaxX N=73, Placebo N=67) [units: mg/dL] Median (Inter-Quartile Range)	107 (88 to 132)	110 (89 to 127)	109 (88 to 130)
Fasting triglycerides (NucleomaxX N=82, Placebo N=81) [units: mg/dL] Median (Inter-Quartile Range)	161 (112 to 237)	165 (114 to 262)	164 (114 to 258)
Hemoglobin [units: g/dL] Median (Inter-Quartile Range)	14.9 (13.7 to 15.6)	15.0 (14.0 to 15.8)	14.9 (13.8 to 15.7)
Leukocytes [units: cells*10^3/L] Median (Inter-Quartile Range)	5.6 (4.2 to 7.1)	5.5 (4.7 to 7.0)	5.5 (4.5 to 7.0)
Creatine kinase (NucleomaxX N=80, Placebo N=82) [units: IU/L] Median (Inter-Quartile Range)	125 (79 to 216)	142 (88 to 247)	134 (84 to 231)

Outcome Measures

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1. Primary:

Change in Limb Fat (g) From Baseline [ Time Frame: Baseline and Week 48 ]

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2. Secondary:

Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities) [ Time Frame: Through Week 48 ]

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3. Secondary:

Number of Subjects Discontinuing Study Medication [ Time Frame: Through Week 48 ]

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4. Secondary:

Change in Limb Fat From Baseline (Week 24 - Baseline) [ Time Frame: Baseline and Week 24 ]

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5. Secondary:

HIV-1 RNA Level [ Time Frame: At Week 48 ]

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6. Secondary:

Change in CD4+ Count From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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7. Secondary:

Change in Fasting Lactate From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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8. Secondary:

Change in Fasting Glucose From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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9. Secondary:

Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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10. Secondary:

Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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11. Secondary:

Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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12. Secondary:

Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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13. Secondary:

Change in Fasting Triglycerides From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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14. Secondary:

Change in Hemoglobin From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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15. Secondary:

Change in Leukocytes From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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16. Secondary:

Change in Creatine Kinase From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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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: ClinicalTrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu

Publications of Results:

McComsey GA, Walker UA, Budhathoki CB, Su Z, Currier JS, Kosmiski L, Naini LG, Charles S, Medvik K, Aberg JA; AIDS Clinical Trials Group A5229 Team. Uridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229. AIDS. 2010 Oct 23;24(16):2507-15. doi: 10.1097/QAD.0b013e32833ea9bc.

Other Publications:

Koch EC, Schneider J, Weis R, Penning B, Walker UA. Uridine excess does not interfere with the antiretroviral efficacy of nucleoside analogue reverse transcriptase inhibitors. Antivir Ther. 2003 Oct;8(5):485-7.

McComsey GA, Walker UA. Role of mitochondria in HIV lipoatrophy: insight into pathogenesis and potential therapies. Mitochondrion. 2004 Jul;4(2-3):111-8.

Nolan D, Hammond E, Martin A, Taylor L, Herrmann S, McKinnon E, Metcalf C, Latham B, Mallal S. Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy. AIDS. 2003 Jun 13;17(9):1329-38.

Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther. 2005;10 Suppl 2:M117-23. Review.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00307164 History of Changes
Other Study ID Numbers:	A5229 10136 ( Registry Identifier: DAIDS ES ) ACTG A5229
Study First Received:	March 23, 2006
Results First Received:	August 23, 2011
Last Updated:	November 25, 2013
Health Authority:	United States: Food and Drug Administration

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