MedPath

Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

Phase 2
Completed
Conditions
HIV Infections
Lipoatrophy
Interventions
Drug: NucleomaxX
Drug: NucleomaxX placebo
Registration Number
NCT00307164
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
167
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NucleomaxXNucleomaxXParticipants received NucleomaxX for 48 weeks
PlaceboNucleomaxX placeboParticipants received NucleomaxX placebo for 48 weeks
Primary Outcome Measures
NameTimeMethod
Change in Limb Fat (g) From BaselineBaseline 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.

Secondary Outcome Measures
NameTimeMethod
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 Creatine Kinase From Baseline (Week 48 - Baseline)Baseline and Week 48
Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities)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

Number of Subjects Discontinuing Study MedicationThrough Week 48

Number of eligible subjects who discontinued study medication during the study period.

Change in Limb Fat From Baseline (Week 24 - Baseline)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.

HIV-1 RNA LevelAt 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 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

Trial Locations

Locations (30)

Harbor-UCLA Med. Ctr. CRS

🇺🇸

Torrance, California, United States

Univ. of Rochester ACTG CRS

🇺🇸

Rochester, New York, United States

HIV Prevention & Treatment CRS

🇺🇸

New York, New York, United States

Stanford CRS

🇺🇸

Palo Alto, California, United States

Cornell CRS

🇺🇸

New York, New York, United States

The Miriam Hosp. ACTG CRS

🇺🇸

Providence, Rhode Island, United States

The Ponce de Leon Ctr. CRS

🇺🇸

Atlanta, Georgia, United States

Beth Israel Med. Ctr., ACTU

🇺🇸

New York, New York, United States

Univ. of Hawaii at Manoa, Leahi Hosp.

🇺🇸

Honolulu, Hawaii, United States

University of Colorado Hospital CRS

🇺🇸

Aurora, Colorado, United States

Puerto Rico-AIDS CRS

🇵🇷

San Juan, Puerto Rico

Rush Univ. Med. Ctr. ACTG CRS

🇺🇸

Chicago, Illinois, United States

MetroHealth CRS

🇺🇸

Cleveland, Ohio, United States

Pitt CRS

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Washington AIDS CRS

🇺🇸

Seattle, Washington, United States

Vanderbilt Therapeutics CRS

🇺🇸

Nashville, Tennessee, United States

Alabama Therapeutics CRS

🇺🇸

Birmingham, Alabama, United States

Ucsd, Avrc Crs

🇺🇸

San Diego, California, United States

USC CRS

🇺🇸

Los Angeles, California, United States

NY Univ. HIV/AIDS CRS

🇺🇸

New York, New York, United States

Johns Hopkins Adult AIDS CRS

🇺🇸

Baltimore, Maryland, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

🇺🇸

Indianapolis, Indiana, United States

Case CRS

🇺🇸

Cleveland, Ohio, United States

Univ. of Cincinnati CRS

🇺🇸

Cincinnati, Ohio, United States

University of Minnesota, ACTU

🇺🇸

Minneapolis, Minnesota, United States

UCLA CARE Center CRS

🇺🇸

Los Angeles, California, United States

Unc Aids Crs

🇺🇸

Chapel Hill, North Carolina, United States

The Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

Trillium Health ACTG CRS

🇺🇸

Rochester, New York, United States

Duke Univ. Med. Ctr. Adult CRS

🇺🇸

Durham, North Carolina, United States

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