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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00307164
Other study ID # A5229
Secondary ID 10136ACTG A5229
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date September 2006
Est. completion date December 2008

Study information

Verified date January 2019
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 167
Est. completion date December 2008
Est. primary completion date December 2008
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
NucleomaxX
36 g sachet taken orally three times daily
NucleomaxX placebo
36 g placebo sachet taken orally three times daily

Locations

Country Name City State
Puerto Rico Puerto Rico-AIDS CRS San Juan
United States The Ponce de Leon Ctr. CRS Atlanta Georgia
United States University of Colorado Hospital CRS Aurora Colorado
United States Johns Hopkins Adult AIDS CRS Baltimore Maryland
United States Alabama Therapeutics CRS Birmingham Alabama
United States Unc Aids Crs Chapel Hill North Carolina
United States Rush Univ. Med. Ctr. ACTG CRS Chicago Illinois
United States Univ. of Cincinnati CRS Cincinnati Ohio
United States Case CRS Cleveland Ohio
United States MetroHealth CRS Cleveland Ohio
United States The Ohio State University Medical Center Columbus Ohio
United States Duke Univ. Med. Ctr. Adult CRS Durham North Carolina
United States Univ. of Hawaii at Manoa, Leahi Hosp. Honolulu Hawaii
United States Indiana Univ. School of Medicine, Infectious Disease Research Clinic Indianapolis Indiana
United States UCLA CARE Center CRS Los Angeles California
United States USC CRS Los Angeles California
United States University of Minnesota, ACTU Minneapolis Minnesota
United States Vanderbilt Therapeutics CRS Nashville Tennessee
United States Beth Israel Med. Ctr., ACTU New York New York
United States Cornell CRS New York New York
United States HIV Prevention & Treatment CRS New York New York
United States NY Univ. HIV/AIDS CRS New York New York
United States Stanford CRS Palo Alto California
United States Pitt CRS Pittsburgh Pennsylvania
United States The Miriam Hosp. ACTG CRS Providence Rhode Island
United States Trillium Health ACTG CRS Rochester New York
United States Univ. of Rochester ACTG CRS Rochester New York
United States Ucsd, Avrc Crs San Diego California
United States University of Washington AIDS CRS Seattle Washington
United States Harbor-UCLA Med. Ctr. CRS Torrance California

Sponsors (1)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

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. — View Citation

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 — View Citation

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

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. — View Citation

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
Secondary Number of Subjects Discontinuing Study Medication Number of eligible subjects who discontinued study medication during the study period. Through Week 48
Secondary 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
Secondary HIV-1 RNA Level At Week 48
Secondary Change in CD4+ Count From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting Lactate From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting Glucose From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Fasting Triglycerides From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Hemoglobin From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Leukocytes From Baseline (Week 48 - Baseline) Baseline and Week 48
Secondary Change in Creatine Kinase From Baseline (Week 48 - Baseline) Baseline and Week 48
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