HIV InfectionsPhase 2NCT00119379

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

A Phase 2 study testing NucleomaxX and Tenofovir Disoproxil Fumarate in people with HIV Infections and Lipodystrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV Infections, Lipodystrophy, Metabolic Diseases
What is being tested?: NucleomaxX and Tenofovir Disoproxil Fumarate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteUnited States
Study dates: Apr 2005to Oct 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University Hospitals of Cleveland
Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: HIV Infections, Lipodystrophy, Metabolic Diseases, Nutrition Disorders
Being tested: NucleomaxX, Tenofovir Disoproxil Fumarate
Keywords: lipoatrophy, mitochondria, HIV, treatment experienced
Medical subject headings: HIV Infections, Lipodystrophy, Metabolic Diseases, Nutrition Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NucleomaxXDrug
Also called uridine
NucleomaxX 36 grams TID every other day
Tenofovir Disoproxil FumarateDrug
Also called TDF
Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate

Study groups in NCT00119379
Study group	Role	What they receive
uridine supplementation	Experimental	NucleomaxX 36 grams TID every other day Receives: Drug: NucleomaxX
Switch to Tenofovir	Active comparator	Switch of AZT or d4T to Tenofovir Disoproxil Fumarate Receives: Drug: Tenofovir Disoproxil Fumarate

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (4)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2005Oct 2008

First posted13 Jul 2005 (estimated)
Study startApr 2005
Primary completionOct 2008
Study completionOct 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00119379
Sponsor's protocol ID: 1R01AI060484-01A2B
Other IDs: R01AI060484
Status last verified: May 2017
First submitted: 11 Jul 2005
Last updated: 7 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

McComsey GA, O'Riordan M, Setzer B, Lebrecht D, Baron E, Walker UA. Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices. Eur J Clin Nutr. 2008 Aug;62(8):1031-7. doi: 10.1038/sj.ejcn.1602793. Epub 2007 May 30.
PubMed 17538545
McComsey GA, O'Riordan M, Choi J, Libutti D, Rowe D, Storer N, Harrill D, Gerschenson M. Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir. Antivir Ther. 2012;17(2):347-53. doi: 10.3851/IMP1928. Epub 2011 Oct 13.
PubMed 22293126

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy
ClinicalTrials.gov ID: NCT00119379
Acronym / sponsor ID: 1R01AI060484-01A2B
Conditions: HIV Infections, Lipodystrophy, Metabolic Diseases, Nutrition Disorders
Keywords: lipoatrophy, mitochondria, HIV, treatment experienced
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Apr 2005
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 13 Jul 2005 (estimated)
Results: Posted 12 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
uridine supplementation	Experimental	Drug: NucleomaxXNucleomaxX 36 grams TID every other day
Switch to Tenofovir	Active comparator	Drug: Tenofovir Disoproxil FumarateSwitch of AZT or d4T to Tenofovir Disoproxil Fumarate

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NucleomaxXAlso: uridineNucleomaxX 36 grams TID every other day	Drug	uridine supplementation
Tenofovir Disoproxil FumarateAlso: TDFSwitch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate	Drug	Switch to Tenofovir

Primary outcome

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

4 secondary outcomes

Change in Limb Fat
Time frame: Baseline to Week 48
Change in Trunk Fat
Time frame: Baseline to Week 48
Change in Lumbar Spine Bone Mineral Density (BMD)
Time frame: Baseline to Week 48
Change in Hip Bone Mineral Density (BMD)
Time frame: Baseline to Week 48

Results and safety

Results posted to the registry on 12 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Uridine Supplementation	26	22
Switch to TDF	24	23

Primary outcome: Change in Fat mtDNA Content

Time frame: Baseline to Week 48. Median (Inter-Quartile Range). Unit: copies/cell

Measure	Uridine Supplementation n = 26	Switch to TDF n = 24
Value	-169 (-778 to 64)	321 (-298 to 669)

Primary outcome: Change in PBMC mtDNA

Time frame: Baseline to Week 48. Median (Inter-Quartile Range). Unit: copies/cell

Measure	Uridine Supplementation n = 26	Switch to TDF n = 24
Value	-24 (-158 to 91)	-52 (-105 to 108)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Weeks 4,8,12,18 and 36. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Uridine Supplementation	8 of 26 (30.8%)	18 of 26 (69.2%)	0 of 26
Switch to TDF	6 of 24 (25%)	13 of 24 (54.2%)	0 of 24

Limitations and caveats (from the sponsor): Small sample size; Lack of control arm where tNRTI therapy was continued without any intervention; Adherence measured by sachet/pill count method.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 17538545McComsey GA, O'Riordan M, Setzer B, Lebrecht D, Baron E, Walker UA. Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices. Eur J Clin Nutr. 2008 Aug;62(8):1031-7. doi: 10.1038/sj.ejcn.1602793. Epub 2007 May 30.
Derived from this study: PubMed 22293126McComsey GA, O'Riordan M, Choi J, Libutti D, Rowe D, Storer N, Harrill D, Gerschenson M. Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir. Antivir Ther. 2012;17(2):347-53. doi: 10.3851/IMP1928. Epub 2011 Oct 13.
click here for more information about uridine supplementation or switch to tenofovir.Link provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Grace A. McComsey, MD principal investigator

Case Western Reserve University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Fat mtDNA Content (time frame: Baseline to Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00119379, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.