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

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Lipodystrophy
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Brief Title

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

Official Title

Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy

Brief Summary

      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.

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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Change in Fat mtDNA Content

Secondary Outcome

 Change in Limb Fat

Condition

HIV Infections

Intervention

NucleomaxX

Study Arms / Comparison Groups

 uridine supplementation
Description:  NucleomaxX 36 grams TID every other day

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

50

Start Date

April 2005

Completion Date

October 2008

Primary Completion Date

October 2008

Eligibility Criteria

        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

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Grace A. McComsey, MD, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT00119379

Organization ID

1R01AI060484-01A2B

Secondary IDs

R01AI060484

Responsible Party

Principal Investigator

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Study Sponsor

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

Verification Date

May 2017