Neurotropin Treatment of Fibromyalgia

• ClinicalTrials.gov Identifier: NCT00366535
• Recruitment Status: Completed
• First Posted: August 21, 2006
• Results First Posted: June 4, 2018
• Last Update Posted: June 27, 2018
• Sponsor: National Institute of Nursing Research (NINR)
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health Clinical Center (CC); University of Michigan; National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Fibromyalgia
• Interventions: Drug: Placebo; Drug: Neurotropin
• Enrollment: 56

Participant Flow

Recruitment Details	Most patients were recruited by direct physician referral or through the Patient Recruitment and Public Liaison (PRPL) office. Potential subjects were screened for study eligibility at the NIH Clinical Center.
Pre-assignment Details	Patients with abnormal screening laboratory tests or had positive HIV test were excluded from study participation. Women who had positive urine pregnancy test were also excluded. Also patients with traumatic or non-traumatic pain disorders or had neurocognitive impairment making it challenging to obtain informed consent, were also excluded.

Arm/Group Title	Study Drug A Then Study Drug B (G-1)	Study Drug B First, Then Study Drug A (G-2)
Arm/Group Description	Double blind cross-over study: received Placebo (4 tabs, b.i.d.) for 12 weeks and then Neurotropin (4 tabs, b.i.d.) for 12 weeks (after at least 1 week washout period). Assignment to each group was randomized by the NIH Clinical Center pharmacy. Study team and participants were all blinded.	Double blind cross-over study: received Study drug B (4 tabs, b.i.d.) for 12 weeks and then Study drug A (4 tabs, b.i.d.) for 12 weeks (after at least 1 week washout period). Assignment to each group was randomized by the NIH CC pharmacy. Study team and participants were blinded.
Period Title: First Phase: 12 Weeks
Started	27	29
Completed	24	21
Not Completed	3	8
Reason Not Completed
Adverse Event	1	3
Withdrawal by Subject	2	5
Period Title: Washout Period (at Least a Week)
Started	24	21
Completed	24	21
Not Completed	0	0
Period Title: Second Phase: 12 Weeks
Started	24	21
Completed	21	18
Not Completed	3	3
Reason Not Completed
Adverse Event	1	1
Withdrawal by Subject	2	2

Baseline Characteristics

Arm/Group Title		Placebo First, Then Neurotropin (G-1)	Neurotropin First, Then Placebo (G-2)	Total
Arm/Group Description		Double blind cross-over study: receive Placebo (4 tabs, b.i.d.) for 12 weeks and then Neurotropin (4 tabs, b.i.d.) for 12 weeks (after at least 1 week washout period). Assignment to each group was in random order, selected by the pharmacy with all others blind.	Double blind cross-over study: receive Neurotropin (4 tabs, b.i.d.) for 12 weeks and then Placebo (4 tabs, b.i.d.) for 12 weeks (after at least 1 week washout period). Assignment to each group was in random order, selected by the pharmacy with all others blind.	Total of all reporting groups
Overall Number of Baseline Participants		29	27	56
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	29 participants	27 participants	56 participants
	<=18 years	0	0	0
	Between 18 and 65 years	27	27	54
	>=65 years	2	0	2
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	29 participants	27 participants	56 participants
		45.6 (12.6)	41.7 (12.9)	44.3 (12.8)
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	29 participants	27 participants	56 participants
	Female	29	27	56
	Male	0	0	0
		[1] Measure Description: Because fibromyalgia is much more common in women and because there are significant gender differences in the clinical characteristics of the disorder, only women will be included in the study.
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	29 participants	27 participants	56 participants
	American Indian or Alaska Native	0	0	0
	Asian	0	0	0
	Native Hawaiian or Other Pacific Islander	0	0	0
	Black or African American	2	5	7
	White	27	20	47
	More than one race	0	1	1
	Unknown or Not Reported	0	1	1
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	29 participants	27 participants	56 participants
		29	27	56

Outcome Measures

1. Primary Outcome

Title	Fibromyalgia Impact Questionnaire
Description	The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item self-administered measure to assess 3 areas of fibromyalgia (FM): function, overall impact, and symptoms. The total FIQ score was the primary outcome of the study. The total FIQ score is the sum of the 3 areas measured in the FIQ. The maximum possible total FIQ score is 100, with a minimum score of 10. The average FM patient scores about 50, severely afflicted FM patients are usually 70 and above. Data analysis is ongoing from data collected from study completers.
Time Frame	25 weeks

Outcome Measure Data

Analysis Population Description

Total 56 patients enrolled, and 39 patients completed the study. 17 patients withdrawn from the study. Three of 39 patients were excluded from the data analysis because there had missing FIQ scores at Baseline and/or Week 12. The data from the study of the 36 participants with complete data sets was analyzed.

Arm/Group Title	FIQ Before Placebo Treatment First in G-1	FIQ After Placebo Treatment First in G-1	FIQ Before Neurotropin Treatment Second in G-1	FIQ After Neurotropin Treatment Second in G-1	FIQ Before Neurotropin Treatment First in G-2	FIQ After Neurotropin Treatment First in G-2	FIQ Before Placebo Treatment Second in G-2	FIQ After Placebo Treatment Second in G-2
Arm/Group Description:	FIQ of this group was determined before the 12 week-treatment with Placebo.	This group received Placebo 4 tabs b.i.d. for 12 weeks first. FIQ was determined at the end of the 12 week-treatment with Placebo.	FIQ of this group was determined before the 12 week-treatment with Neurotropin.	This group received Neurotropin 4 tabs b.i.d. for 12 weeks after at least 1 week "washout" period following the first 12 week interval on placebo. FIQ was determined at the end of the 12 week-treatment with Neurotropin.	FIQ of this group was determined before the 12 week-treatment with Neurotropin.	This group received Neurotropin 4 tabs b.i.d. for 12 weeks first. FIQ was determined at the end of the 12 week-treatment with Placebo.	FIQ of this group was determined before the 12 week-treatment with Placebo.	This group received Placebo 4 tabs b.i.d. for 12 weeks after at least 1 week "washout" period following the first 12 week interval on placebo. FIQ was determined at the end of the 12 week-treatment with Placebo.
Overall Number of Participants Analyzed	20	20	20	20	16	16	16	16
Mean (Standard Deviation); Unit of Measure: units on a scale
	49.9 (1.8)	37.5 (3.7)	39.9 (3.4)	33.4 (4.1)	47.7 (2.1)	28.8 (4.5)	30.1 (4.1)	32.8 (3.6)

Adverse Events

Time Frame	The adverse event data was collected during the study period for 6 to 7 months.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo Treatment First in G-1		Neurotropin Treatment Second in G-1		Neurotropin Treatment First in G-2		Placebo Treatment Second in G-2
Arm/Group Description	This group received Placebo 4 tabs b.i.d. for the first 12 weeks.		This group received Neurotropin 4 tabs b.i.d. for 12 weeks after at least 1 week "washout" period following the first 12 week interval on Placebo.		This group received Neurotropin 4 tabs b.i.d. for the first 12 weeks.		This group received Placebo 4 tabs b.i.d. for 12 weeks after at least 1 week "washout" period following the first 12 week interval on Neurotropin.
All-Cause Mortality
	Placebo Treatment First in G-1		Neurotropin Treatment Second in G-1		Neurotropin Treatment First in G-2		Placebo Treatment Second in G-2
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/56 (0.00%)		0/29 (0.00%)		0/27 (0.00%)		0/27 (0.00%)
Serious Adverse Events
	Placebo Treatment First in G-1		Neurotropin Treatment Second in G-1		Neurotropin Treatment First in G-2		Placebo Treatment Second in G-2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0.00%)		0/29 (0.00%)		0/27 (0.00%)		0/27 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo Treatment First in G-1		Neurotropin Treatment Second in G-1		Neurotropin Treatment First in G-2		Placebo Treatment Second in G-2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/56 (5.36%)		1/29 (3.45%)		3/27 (11.11%)		1/27 (3.70%)
Cardiac disorders
Chest pain and Abnormal HB * [1]	1/56 (1.79%)	1	0/29 (0.00%)	0	2/27 (7.41%)	2	0/27 (0.00%)	0
Hepatobiliary disorders
Abnormality of liver function test * [2]	1/56 (1.79%)	1	0/29 (0.00%)	0	0/27 (0.00%)	0	0/27 (0.00%)	0
Musculoskeletal and connective tissue disorders
Pain * [3]	1/56 (1.79%)	1	1/29 (3.45%)	1	0/27 (0.00%)	0	1/27 (3.70%)	1
Nervous system disorders
Dizziness * [4]	0/56 (0.00%)	0	0/29 (0.00%)	0	1/27 (3.70%)	1	0/27 (0.00%)	0
* Indicates events were collected by non-systematic assessment; [1] Chest pain followed by dizziness, shortness of breath and weakness, abnormal heart beat; [2] Increased in plasma levels of ALT, AST and LDH, and creatinine kinase; [3] Increased of pain; [4] Caused dizziness, headache and difficulty walking

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Leorey Saligan, Chief
• Organization: Symptoms Biology Unit, DIR, NINR, NIH
• Phone: 301-451-1685
• EMail: saliganl@mail.nih.gov

Publications:

Dworkin RH, Fields HL. Fibromyalgia from the perspective of neuropathic pain. J Rheumatol Suppl. 2005 Aug;75:1-5. Review.

Rowbotham MC. Is fibromyalgia a neuropathic pain syndrome? J Rheumatol Suppl. 2005 Aug;75:38-40. Review.

Crofford LJ. The relationship of fibromyalgia to neuropathic pain syndromes. J Rheumatol Suppl. 2005 Aug;75:41-5. Review.

• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )
• ClinicalTrials.gov Identifier: NCT00366535
• Other Study ID Numbers: 060229; 06-NR-0229 ( Other Identifier: NIH )
• First Submitted: August 18, 2006
• First Posted: August 21, 2006
• Results First Submitted: August 21, 2017
• Results First Posted: June 4, 2018
• Last Update Posted: June 27, 2018