Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults

May 15, 2017 updated by: Grace McComsey, National Institute of Allergy and Infectious Diseases (NIAID)

Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy

HIV lipoatrophy is a condition marked by fat loss; it occurs in many patients taking antiretroviral (ARV) therapy that includes nucleoside reverse transcriptase inhibitors (NRTIs). Lipoatrophy may be related to mitochondrial toxicity, a condition that can damage the heart, nerves, muscles, kidneys, and liver, and can affect the body's ability to produce energy. NucleomaxX is a food supplement consisting of a sugar cane extract high in nucleosides, which are building blocks that may counteract the negative effects of NRTIs. Tenofovir disoproxil fumarate (TDF) is an NRTI that may cause less lipoatrophy than other drugs in its class, such as zidovudine (ZDV) or stavudine (d4T). The purpose of this study is to determine whether nucleoside supplementation with NucleomaxX and substitution of TDF for ZDV or d4T in an ARV regimen can reverse fat loss caused by mitochondrial toxicity in HIV infected adults.

Study hypotheses: 1) The substitution of TDF for d4T or ZDV in patients with HIV lipoatrophy will result in an increase in mitochondrial DNA content in fat, skeletal muscle, and peripheral blood mononuclear cells (PBMCs), which in turn will lead to an improvement in mitochondrial function as assessed by electron transport chain (ETC) and oxidative phosphorylation pathway (OXPHOS) activity. The latter should lead to a decrease in fat apoptosis and in mitochondrial and lipid oxidative damage biomarkers. 2) Supplementation with uridine (via NucleomaxX) will increase mtDNA content in adipose tissue and increase body fat content.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

NRTIs are an important part of many ARV regimens used to treat HIV infected patients; however, the relationship between NRTI-induced mitochondrial dysfunction and lipoatrophy is still unclear and requires additional research. Additionally, the relationship between the gain in dual-energy x-ray absorptiometry (DEXA)-measured limb fat and mitochondrial DNA (mtDNA) content, mitochondrial function, fat apoptosis, and oxidative damage will also be examined in this study.

Patients will participate in this study for 48 weeks. Participants will be randomly assigned to one of two groups. Group 1 patients will receive NucleomaxX every other day. Group 2 patients will substitute TDF for ZDV or d4T every day in their current stable NRTI-containing ARV regimen. NucleomaxX will be provided to Group 1 patients, but TDF or any other ARV will not be provided by this study.

There will be 10 study visits, which will occur at study entry and Weeks 2, 4, 8, 12, 18, 24, 30, 36, and 48. Blood collection will occur at all visits. Additionally, urine collection, DEXA scans, and fat biopsies will be done at study entry and Weeks 24 and 48.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of HIV lipoatrophy
  • Receiving a stable stavudine- or zidovudine-containing ARV regimen
  • HIV-1 RNA viral load less than 50 copies/ml

Exclusion Criteria:

  • Coagulopathies or other bleeding disorders
  • Diabetes requiring medication
  • Creatinine clearance less than 50 ml/min
  • Pregnancy or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: uridine supplementation
NucleomaxX 36 grams TID every other day
Drug: NucleomaxX
NucleomaxX 36 grams TID every other day
Other Names:
  • uridine
Active Comparator: Switch to Tenofovir
Switch of AZT or d4T to Tenofovir Disoproxil Fumarate
Drug: Tenofovir Disoproxil Fumarate
Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate
Other Names:
  • TDF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fat mtDNA Content
Time Frame: Baseline to Week 48
Subcutaneous abdominal fat mitochondrial DNA (mtDNA)
Baseline to Week 48
Change in PBMC mtDNA
Time Frame: Baseline to Week 48
Peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA), measured in copies/cell
Baseline to Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Limb Fat
Time Frame: Baseline to Week 48
Change in limb fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Baseline to Week 48
Change in Trunk Fat
Time Frame: Baseline to Week 48
Change in trunk fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Baseline to Week 48
Change in Lumbar Spine Bone Mineral Density (BMD)
Time Frame: Baseline to Week 48
Change in lumbar spine bone mineral density (BMD) as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Baseline to Week 48
Change in Hip Bone Mineral Density (BMD)
Time Frame: Baseline to Week 48
Change in hip bone mineral density (BMD) as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Baseline to Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Grace A. McComsey, MD, Case Western Reserve University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2005

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

July 11, 2005

First Submitted That Met QC Criteria

July 11, 2005

First Posted (Estimate)

July 13, 2005

Study Record Updates

Last Update Posted (Actual)

June 7, 2017

Last Update Submitted That Met QC Criteria

May 15, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01AI060484-01A2B
  • R01AI060484 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metabolic Diseases

Clinical Trials on NucleomaxX

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe