Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

NCT ID: NCT00307164

Last Updated: 2021-11-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

167 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-09-30

Study Completion Date

2008-12-31

Brief Summary

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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

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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.

Conditions

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HIV Infections Lipoatrophy

Keywords

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Treatment Experienced Uridine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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NucleomaxX

Participants received NucleomaxX for 48 weeks

Group Type ACTIVE_COMPARATOR

NucleomaxX

Intervention Type DRUG

36 g sachet taken orally three times daily

Placebo

Participants received NucleomaxX placebo for 48 weeks

Group Type PLACEBO_COMPARATOR

NucleomaxX placebo

Intervention Type DRUG

36 g placebo sachet taken orally three times daily

Interventions

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NucleomaxX

36 g sachet taken orally three times daily

Intervention Type DRUG

NucleomaxX placebo

36 g placebo sachet taken orally three times daily

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Grace A. McComsey, MD

Role: STUDY_CHAIR

Division of Infectious Diseases, Case Western Reserve University

Judith A. Aberg, MD

Role: STUDY_CHAIR

New York University

Locations

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Alabama Therapeutics CRS

Birmingham, Alabama, United States

Site Status

USC CRS

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Stanford CRS

Palo Alto, California, United States

Site Status

Ucsd, Avrc Crs

San Diego, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

The Ponce de Leon Ctr. CRS

Atlanta, Georgia, United States

Site Status

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

Beth Israel Med. Ctr., ACTU

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Cornell CRS

New York, New York, United States

Site Status

HIV Prevention & Treatment CRS

New York, New York, United States

Site Status

Trillium Health ACTG CRS

Rochester, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

MetroHealth CRS

Cleveland, Ohio, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Pitt CRS

Pittsburgh, Pennsylvania, United States

Site Status

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States

Site Status

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Puerto Rico-AIDS CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 14640397 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16120376 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12799554 (View on PubMed)

Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther. 2005;10 Suppl 2:M117-23.

Reference Type BACKGROUND
PMID: 16152713 (View on PubMed)

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.

Reference Type RESULT
PMID: 20827170 (View on PubMed)

Other Identifiers

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10136

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5229

Identifier Type: -

Identifier Source: secondary_id

A5229

Identifier Type: -

Identifier Source: org_study_id