HIV InfectionsPhase 2/3NCT00307164
Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy
A Phase 2/3 study testing NucleomaxX in people with HIV Infections and Lipoatrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 30 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Lipoatrophy
- What is being tested?
- NucleomaxX
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 167 participants
- Where
- 30 sitesin 2 countries
- Study dates
- Sep 2006to Dec 2008
- Phase
- Phase 2/3
- 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
- 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
Who cannot join
- 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.
Show all 17Show fewer
- 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
Trial locations and contacts
30 sites in 2 countries.
30 sites in 2 countries
United States29 sites
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308
University of Colorado Hospital CRS
Aurora, Colorado, 80262-3706
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287-8106
Alabama Therapeutics CRS
Birmingham, Alabama, 35924-2050
Unc Aids Crs
Chapel Hill, North Carolina, 27514
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612
Univ. of Cincinnati CRS
Cincinnati, Ohio, 45267-0405
Case CRS
Cleveland, Ohio, 44106-5083
MetroHealth CRS
Cleveland, Ohio, 44109
The Ohio State University Medical Center
Columbus, Ohio, 43210
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202-5250
USC CRS
Los Angeles, California, 90033
UCLA CARE Center CRS
Los Angeles, California
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455
Vanderbilt Therapeutics CRS
Nashville, Tennessee, 37203
Beth Israel Med. Ctr., ACTU
New York, New York, 10003
NY Univ. HIV/AIDS CRS
New York, New York, 10016-6481
Cornell CRS
New York, New York, 10021
HIV Prevention & Treatment CRS
New York, New York, 10032
Stanford CRS
Palo Alto, California, 94305-5107
Pitt CRS
Pittsburgh, Pennsylvania, 15213-2582
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, 02906
Trillium Health ACTG CRS
Rochester, New York, 14607
Univ. of Rochester ACTG CRS
Rochester, New York, 14642-0001
Ucsd, Avrc Crs
San Diego, California, 92103
University of Washington AIDS CRS
Seattle, Washington, 98104
Harbor-UCLA Med. Ctr. CRS
Torrance, California, 90502-2052
About this study
Official title: A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy
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.
Read the 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, 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
- HIV Infections, Lipoatrophy
- Being tested
- NucleomaxX, NucleomaxX placebo
- Keywords
- Treatment Experienced, Uridine
- Medical subject headings
- HIV Infections, Lipodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NucleomaxXDrug
36 g sachet taken orally three times daily
NucleomaxX placeboDrug
36 g placebo sachet taken orally three times daily
| Study group | Role | What they receive |
|---|---|---|
| NucleomaxX | Active comparator | Participants received NucleomaxX for 48 weeks Receives: Drug: NucleomaxX |
| Placebo | Placebo comparator | Participants received NucleomaxX placebo for 48 weeks Receives: Drug: NucleomaxX placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Limb Fat (g) From Baseline
Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups.
Measured: Baseline and Week 48
Secondary outcomes (15)
Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities)
Time to safety events (grade 3 [Severe] or 4 [life-threatening] sign/symptom or laboratory-based abnormality that is at least one grade higher than baseline) from study entry
Measured: Through Week 48
Number of Subjects Discontinuing Study Medication
Number of eligible subjects who discontinued study medication during the study period.
Measured: Through Week 48
Change in Limb Fat From Baseline (Week 24 - Baseline)
Limb fat was measured at baseline and visit week 24 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 24 (week 24 - baseline) was estimated for the treatment groups.
Measured: Baseline and Week 24
HIV-1 RNA Level
Measured: At Week 48
Change in CD4+ Count From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting Lactate From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting Glucose From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Fasting Triglycerides From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Hemoglobin From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Leukocytes From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Change in Creatine Kinase From Baseline (Week 48 - Baseline)
Measured: Baseline and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2006 (estimated)
- Study startSep 2006
- Primary completionDec 2008
- Study completionDec 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 (5)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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Grace A. McComsey, MD, Study chair, Division of Infectious Diseases, Case Western Reserve UniversityJudith A. Aberg, MD, Study chair, New York University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00307164
- Sponsor's protocol ID
- A5229
- Other IDs
- 10136, ACTG A5229
- Status last verified
- Jan 2019
- First submitted
- 23 Mar 2006
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 14640397McComsey 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.
PubMed 16120376Nolan 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.
PubMed 12799554Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther. 2005;10 Suppl 2:M117-23.
PubMed 16152713McComsey 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.
PubMed 20827170
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy
- ClinicalTrials.gov ID
- NCT00307164
- Acronym / sponsor ID
- A5229
- Conditions
- HIV Infections, Lipoatrophy
- Keywords
- Treatment Experienced, Uridine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 27 Mar 2006 (estimated)
- Results
- Posted 4 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NucleomaxX | Active comparator | Drug: NucleomaxXParticipants received NucleomaxX for 48 weeks |
| Placebo | Placebo comparator | Drug: NucleomaxX placeboParticipants received NucleomaxX placebo for 48 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (17 listed)
- 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
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 |
|---|---|---|
| NucleomaxX36 g sachet taken orally three times daily | Drug | NucleomaxX |
| NucleomaxX placebo36 g placebo sachet taken orally three times daily | Drug | Placebo |
Primary outcome
Change in Limb Fat (g) From Baseline
Time frame: Baseline and Week 48
Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups.
15 secondary outcomes
Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities)
Time frame: Through Week 48
Number of Subjects Discontinuing Study Medication
Time frame: Through Week 48
Change in Limb Fat From Baseline (Week 24 - Baseline)
Time frame: Baseline and Week 24
HIV-1 RNA Level
Time frame: At Week 48
Change in CD4+ Count From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting Lactate From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting Glucose From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Fasting Triglycerides From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Hemoglobin From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Leukocytes From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Change in Creatine Kinase From Baseline (Week 48 - Baseline)
Time frame: Baseline and Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14640397Koch 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.
- Background: PubMed 16120376McComsey 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.
- Background: PubMed 12799554Nolan 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.
- Background: PubMed 16152713Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther. 2005;10 Suppl 2:M117-23.
- Results publication: PubMed 20827170McComsey 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.
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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 study chair
Division of Infectious Diseases, Case Western Reserve University
Judith A. Aberg, MD study chair
New York University
30 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing NucleomaxX in people with HIV Infections and Lipoatrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 30 sites in 2 countries.
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 7 inclusion and 17 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Puerto Rico. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 4 Oct 2011). 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 Limb Fat (g) From Baseline (time frame: Baseline and Week 48). 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 NCT00307164, which also lists 5 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 4 Nov 2021.