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

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.

Study Overview

Status

Completed

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

Interventional

Enrollment (Actual)

167

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • San Juan, Puerto Rico, 00936-5067
        • Puerto Rico-AIDS CRS
    • Alabama
      • Birmingham, Alabama, United States, 35924-2050
        • Alabama Therapeutics CRS
    • California
      • Los Angeles, California, United States, 90033
        • USC CRS
      • Los Angeles, California, United States
        • UCLA CARE Center CRS
      • Palo Alto, California, United States, 94305-5107
        • Stanford CRS
      • San Diego, California, United States, 92103
        • Ucsd, Avrc Crs
      • Torrance, California, United States, 90502-2052
        • Harbor-UCLA Med. Ctr. CRS
    • Colorado
      • Aurora, Colorado, United States, 80262-3706
        • University of Colorado Hospital CRS
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • The Ponce de Leon Ctr. CRS
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ. of Hawaii at Manoa, Leahi Hosp.
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Univ. Med. Ctr. ACTG CRS
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5250
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21287-8106
        • Johns Hopkins Adult AIDS CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • New York
      • New York, New York, United States, 10003
        • Beth Israel Med. Ctr., ACTU
      • New York, New York, United States, 10021
        • Cornell CRS
      • New York, New York, United States, 10016-6481
        • NY Univ. HIV/AIDS CRS
      • New York, New York, United States, 10032
        • HIV Prevention & Treatment CRS
      • Rochester, New York, United States, 14642-0001
        • Univ. of Rochester ACTG CRS
      • Rochester, New York, United States, 14607
        • Trillium Health ACTG CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Unc Aids Crs
      • Durham, North Carolina, United States, 27710
        • Duke Univ. Med. Ctr. Adult CRS
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0405
        • Univ. of Cincinnati CRS
      • Cleveland, Ohio, United States, 44106-5083
        • Case CRS
      • Cleveland, Ohio, United States, 44109
        • MetroHealth CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213-2582
        • Pitt CRS
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hosp. ACTG CRS
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt Therapeutics CRS
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington AIDS CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
ACTIVE_COMPARATOR: NucleomaxX
Participants received NucleomaxX for 48 weeks
36 g sachet taken orally three times daily
PLACEBO_COMPARATOR: Placebo
Participants received NucleomaxX placebo for 48 weeks
36 g placebo sachet taken orally three times daily

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
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 Frame: Through Week 48
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
Time Frame: Through Week 48
Number of eligible subjects who discontinued study medication during the study period.
Through Week 48
Change in Limb Fat From Baseline (Week 24 - Baseline)
Time Frame: Baseline and Week 24
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
Time Frame: At Week 48
At Week 48
Change in CD4+ Count From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting Lactate From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting Glucose From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Fasting Triglycerides From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Hemoglobin From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Leukocytes From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48
Change in Creatine Kinase From Baseline (Week 48 - Baseline)
Time Frame: Baseline and Week 48
Baseline and Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Grace A. McComsey, MD, Division of Infectious Diseases, Case Western Reserve University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (ACTUAL)

December 1, 2008

Study Completion (ACTUAL)

December 1, 2008

Study Registration Dates

First Submitted

March 23, 2006

First Submitted That Met QC Criteria

March 23, 2006

First Posted (ESTIMATE)

March 27, 2006

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2021

Last Update Submitted That Met QC Criteria

November 2, 2021

Last Verified

January 1, 2019

More Information

Terms related to this study

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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