Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

HIV Infections Clinical Trial

Official title:

A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy

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
• 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
• 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

Related Conditions & MeSH terms

• HIV Infections
• Lipoatrophy
• Lipodystrophy

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

External Links

•   Click here for more information on lactic acidosis
•   Click here for more information on lipodystrophy
•   Haga clic aquí para ver información sobre este ensayo clínico en español.