Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00307164

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 is 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	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy

Resource links provided by NLM:

MedlinePlus related topics: AIDS Dietary Supplements

Drug Information available for: Uridine

U.S. FDA Resources

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

Primary Outcome Measures:

Change in bone densitometry (DEXA)-measured limb fat [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Signs and symptoms, laboratory-based toxicity, and discontinuation rates of the regimens [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Change in DEXA-measured limb fat [ Time Frame: Through Week 24 ] [ Designated as safety issue: No ]
Change in HIV RNA and CD4 count [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in level of venous lactate [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in level of fasting lipids [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in level of plasma F2 isoprostanes, PBMC MDA and common deletion mitochondrial DNA [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in level of fasting glucose and insulin [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in PBMC mitochondrial DNA [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in PBMC endogenous nucleoside pools [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
Change in hemoglobin, leukocytes, and creatine kinase [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]

Estimated Enrollment:	164
Study Start Date:	September 2006
Study Completion Date:	September 2009
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive NucleomaxX for 48 weeks	Drug: NucleomaxX 36 g sachet taken orally three times daily
2: Placebo Comparator Participants will receive NucleomaxX placebo for 48 weeks	Drug: NucleomaxX 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, 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 is 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 will evaluate the safety and tolerability of NucleomaxX.

This study will last 48 weeks. Participants will be randomly assigned to 1 of 2 arms. Arm A participants will receive NucleomaxX, while Arm B participants will receive a placebo. Participants in both arms will receive their assigned intervention three times per day, every other day, for the duration of the study. There will be 8 study visits over the 48-week study. Blood collection and a physical exam will occur at all study visits; participants will complete an adherence assessment at most visits. Participants will undergo 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 will occur at selected visits. ART will not be 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

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

Show 41 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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:

Click here for more information on lipodystrophy This link exits the ClinicalTrials.gov site

Click here for more information on lactic acidosis This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

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.

McComsey GA, Walker UA. Role of mitochondria in HIV lipoatrophy: insight into pathogenesis and potential therapies. Mitochondrion. 2004 Jul;4(2-3):111-8.

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.

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

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5229
Study First Received:	March 23, 2006
Last Updated:	September 8, 2009
ClinicalTrials.gov Identifier:	NCT00307164 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Treatment Experienced
Uridine

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on September 11, 2009