- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00307164
Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy
A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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San Juan, Puerto Rico, 00936-5067
- Puerto Rico-AIDS CRS
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Alabama
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Birmingham, Alabama, United States, 35924-2050
- Alabama Therapeutics CRS
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California
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Los Angeles, California, United States, 90033
- USC CRS
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Los Angeles, California, United States
- UCLA CARE Center CRS
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Palo Alto, California, United States, 94305-5107
- Stanford CRS
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San Diego, California, United States, 92103
- Ucsd, Avrc Crs
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Torrance, California, United States, 90502-2052
- Harbor-UCLA Med. Ctr. CRS
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Colorado
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Aurora, Colorado, United States, 80262-3706
- University of Colorado Hospital CRS
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Georgia
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Atlanta, Georgia, United States, 30308
- The Ponce de Leon Ctr. CRS
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Hawaii
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Honolulu, Hawaii, United States, 96816
- Univ. of Hawaii at Manoa, Leahi Hosp.
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Illinois
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Chicago, Illinois, United States, 60612
- Rush Univ. Med. Ctr. ACTG CRS
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Indiana
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Indianapolis, Indiana, United States, 46202-5250
- Indiana Univ. School of Medicine, Infectious Disease Research Clinic
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Maryland
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Baltimore, Maryland, United States, 21287-8106
- Johns Hopkins Adult AIDS CRS
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota, ACTU
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New York
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New York, New York, United States, 10003
- Beth Israel Med. Ctr., ACTU
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New York, New York, United States, 10021
- Cornell CRS
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New York, New York, United States, 10016-6481
- NY Univ. HIV/AIDS CRS
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New York, New York, United States, 10032
- HIV Prevention & Treatment CRS
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Rochester, New York, United States, 14642-0001
- Univ. of Rochester ACTG CRS
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Rochester, New York, United States, 14607
- Trillium Health ACTG CRS
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- Unc Aids Crs
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Durham, North Carolina, United States, 27710
- Duke Univ. Med. Ctr. Adult CRS
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Ohio
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Cincinnati, Ohio, United States, 45267-0405
- Univ. of Cincinnati CRS
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Cleveland, Ohio, United States, 44106-5083
- Case CRS
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Cleveland, Ohio, United States, 44109
- MetroHealth CRS
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Columbus, Ohio, United States, 43210
- The Ohio State University Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213-2582
- Pitt CRS
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Rhode Island
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Providence, Rhode Island, United States, 02906
- The Miriam Hosp. ACTG CRS
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Tennessee
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Nashville, Tennessee, United States, 37203
- Vanderbilt Therapeutics CRS
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Washington
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Seattle, Washington, United States, 98104
- University of Washington AIDS CRS
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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ACTIVE_COMPARATOR: NucleomaxX
Participants received NucleomaxX for 48 weeks
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36 g sachet taken orally three times daily
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PLACEBO_COMPARATOR: Placebo
Participants received NucleomaxX placebo for 48 weeks
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36 g placebo sachet taken orally three times daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Limb Fat (g) From Baseline
Time Frame: Baseline and Week 48
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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.
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Baseline and Week 48
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities)
Time Frame: Through Week 48
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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
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Through Week 48
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Number of Subjects Discontinuing Study Medication
Time Frame: Through Week 48
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Number of eligible subjects who discontinued study medication during the study period.
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Through Week 48
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Change in Limb Fat From Baseline (Week 24 - Baseline)
Time Frame: Baseline and Week 24
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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.
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Baseline and Week 24
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HIV-1 RNA Level
Time Frame: At Week 48
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At Week 48
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Change in CD4+ Count From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting Lactate From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting Glucose From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Fasting Triglycerides From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Hemoglobin From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Leukocytes From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Change in Creatine Kinase From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
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Baseline and Week 48
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Collaborators and Investigators
Investigators
- Study Chair: Grace A. McComsey, MD, Division of Infectious Diseases, Case Western Reserve University
Publications and helpful links
General 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. No abstract available.
- McComsey GA, Walker UA. Role of mitochondria in HIV lipoatrophy: insight into pathogenesis and potential therapies. Mitochondrion. 2004 Jul;4(2-3):111-8. doi: 10.1016/j.mito.2004.05.008.
- 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. doi: 10.1097/00002030-200306130-00007.
- Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther. 2005;10 Suppl 2:M117-23.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- A5229
- 10136 (Other Identifier: CTEP)
- ACTG A5229
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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