Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

Study Overview
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Brief Summary
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Lipoatrophy, the loss of body fat from particular areas of the body, is a common side effect of antiretroviral therapy (ART). The purpose of this study was to determine the effectiveness of uridine supplementation in treating HIV infected individuals on stable ART with lipoatrophy.

Detailed Description
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Lipoatrophy is a distressing long-term complication of ART and is associated with decreased quality of life, an increased risk of cardiovascular disease, and nonadherence to ART. The cause of lipoatrophy in HIV-infected individuals receiving ART is not completely understood. However, past research suggests that mitochondrial toxicity in subcutaneous adipose tissue caused by thymidine analogue nucleoside analogues may be responsible for the development of lipoatrophy. Uridine is a nucleoside that has been shown to be an effective supplement in treating individuals with mitochondrial toxicity. NucleomaxX is a food supplement that consists of mitocnol, a sugar cane extract that has a high content of nucleosides, including uridine. The purpose of this study was to evaluate the effects of uridine supplementation in the form of NucleomaxX on limb fat in HIV-infected individuals receiving stable ART containing stavudine (d4T) or zidovudine (ZDV). In addition, this study evaluated the safety and tolerability of NucleomaxX. This study lasted for 48 weeks. Participants were randomly assigned to one of two treatment arms, stratified by d4T or ZDV use. Arm A participants received NucleomaxX for uridine, while Arm B participants received a placebo for NucleomaxX. Participants in both arms received their assigned intervention three times per day, every other day, for the duration of the study. There were 8 study visits over the 48-week study duration. Blood collection and a physical exam occurred at all study visits, and participants completed an adherence assessment at most visits. Participants underwent dual energy X-ray absorptiometry scans (DEXA) within 14 days prior to or following the screening visit and at other selected visits. Specific fasting tests for glucose and lipid levels occurred at selected visits. ART was not provided by this study.

Official Title
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A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy

Conditions
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HIV Infections, Lipoatrophy

Intervention / Treatment
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* Drug: NucleomaxX
* Drug: NucleomaxX placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected Stable ART containing zidovudine or stavudine for at least 12 consecutive weeks prior to study entry Cumulative ART with zidovudine or stavudine for at least 24 weeks prior to study entry Viral load of 5,000 copies/ml or less within 45 days prior to study entry Lipoatrophy in at least two of the following areas: face, arms, legs, OR buttocks Not planning to add to or change current vitamin supplementation Willing to use acceptable forms of contraception Exclusion Criteria: Life expectancy of less than 12 months Currently enrolled in or planning to enroll in an ART interruption study Plans to change current ART regimen Liver failure at anytime prior to study entry Greater than Grade 2 diarrhea or vomiting within 7 days prior to study entry Current AIDS-defining opportunistic infection or illness. Individuals with cutaneous Kaposi's sarcoma not requiring chemotherapy are not excluded. Currently receiving insulin or oral hypoglycemic products for diabetes mellitus Systemic cancer chemotherapy or immunomodulating agents within 30 days prior to study entry Systemic steroids for a cumulative duration of longer than 4 weeks within the 6 months prior to study entry Known allergy or sensitivity to study drug or any of its components Severe lactose intolerance Current drug or alcohol abuse or dependence Clinically significant illness requiring systemic treatment or hospitalization Chronic disability or serious illness that may affect body composition Received an investigational drug other than NucleomaxX or uridine for lipoatrophy within 30 days prior to study entry Certain abnormal laboratory values Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NucleomaxX<br>Participants received NucleomaxX for 48 weeks | Drug: NucleomaxX<br>* 36 g sachet taken orally three times daily<br>|
| Placebo Comparator: Placebo<br>Participants received NucleomaxX placebo for 48 weeks | Drug: NucleomaxX placebo<br>* 36 g placebo sachet taken orally three times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Limb Fat (g) From Baseline | Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups. | Baseline and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities) | Time to safety events (grade 3 [Severe] or 4 [life-threatening] sign/symptom or laboratory-based abnormality that is at least one grade higher than baseline) from study entry | Through Week 48 | 
| Number of Subjects Discontinuing Study Medication | Number of eligible subjects who discontinued study medication during the study period. | Through Week 48 | 
| Change in Limb Fat From Baseline (Week 24 - Baseline) | Limb fat was measured at baseline and visit week 24 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 24 (week 24 - baseline) was estimated for the treatment groups. | Baseline and Week 24 | 
| HIV-1 RNA Level |  | At Week 48 | 
| Change in CD4+ Count From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting Lactate From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting Glucose From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Fasting Triglycerides From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Hemoglobin From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Leukocytes From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 
| Change in Creatine Kinase From Baseline (Week 48 - Baseline) |  | Baseline and Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Experienced, Uridine