Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00307164
First received: March 23, 2006
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
HIV Infections
Lipoatrophy
Drug: NucleomaxX
Drug: NucleomaxX placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Change in Limb Fat (g) From Baseline [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    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:
  • Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities) [ Time Frame: Through Week 48 ] [ Designated as safety issue: Yes ]
    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 Medication [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
    Number of eligible subjects who discontinued study medication during the study period.

  • Change in Limb Fat From Baseline (Week 24 - Baseline) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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 Level [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
  • Change in CD4+ Count From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting Lactate From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting Glucose From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Fasting Triglycerides From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Hemoglobin From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Leukocytes From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Change in Creatine Kinase From Baseline (Week 48 - Baseline) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]

Enrollment: 167
Study Start Date: September 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: NucleomaxX
Participants received NucleomaxX for 48 weeks
Drug: NucleomaxX
36 g sachet taken orally three times daily
Placebo Comparator: Placebo
Participants received NucleomaxX placebo for 48 weeks
Drug: NucleomaxX placebo
36 g placebo sachet taken orally three times daily

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00307164

  Show 30 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Grace A. McComsey, MD Division of Infectious Diseases, Case Western Reserve University
Study Chair: Judith A. Aberg, MD New York University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00307164     History of Changes
Other Study ID Numbers: A5229, 10136, ACTG A5229
Study First Received: March 23, 2006
Results First Received: August 23, 2011
Last Updated: November 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced
Uridine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 26, 2014