HIV LipodystrophyPhase 2NCT00362440
Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome
A Phase 2 study testing Leptin and Pioglitazone or metformin in people with HIV Lipodystrophy, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to determine whether patients with HIV lipodystrophy (fat wasting) benefit from taking the combination of two drugs, one insulin sensitizer (either metformin or pioglitazone, both diabetes drugs) and leptin (a natural hormone produced by your fat cells). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Lipodystrophy
- What is being tested?
- Leptin and Pioglitazone or metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Jun 2011
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age18 years and above and ability and willingness to give written informed consent
- Documented HIV-1 infection
- At least 6 months of stable cumulative antiretroviral therapy with any available or investigational anti- retroviral medication (protease inhibitor, nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, nucleotide reverse transcriptase inhibitor)
- Lipoatrophy developed after initiating HAART treatment (see criteria below). Leptin levels should be less than 4 ng/ml.
- Insulin resistance, impaired fasting glucose, impaired glucose tolerance or type 2 diabetes developed after starting the antiretroviral medications. These categories are defined, respectively, as fasting insulin level above 15 µIU/ml; fasting serum glucose value above 100 mg/dl; 2-hour serum glucose level during a 75 gram oral glucose tolerance test (OGTT) between 140 and 200 mg/dl; and fasting glucose above 126 mg/dl or random glucose level above 200 mg/dl with presence of the classic symptoms of diabetes, such as polyuria, polydipsia, ketonuria, and rapid weight loss
- Hypertriglyceridemia and/or hypercholesterolemia developed after starting the antiretroviral therapy. These categories are defined as fasting triglycerides greater than 150 mg/dl and LDL cholesterol greater than 130 mg/dl, respectively
Show all 10Show fewer
- Female subjects must have a negative urine pregnancy test before enrollment and must agree to use a barrier contraception i.e. condoms, diaphragm or IUD, with or without a hormonal-based method for the duration of the study. Women who are pregnant or become pregnant during the study and who do not accept some form of contraception will be excluded from the study.
- Patients should have history of peripheral fat wasting of the face (e.g. sunken cheeks), limbs (including prominent veins), and/or buttocks, which developed after the initiation of HAART therapy
- Patients should have physical exam findings of a) facial atrophy - sunken cheeks, sunken temporal regions, and/or prominent temporal veins and b) wasting of fat in periphery, limbs and/or buttocks (including prominent veins)
- Patients should have anthropometric measurements suggestive of decreased subcutaneous fat content: Decreased triceps skinfold thickness (< 4 mm in men and < 8 mm in women) or Decreased upper arm circumference (< 27.1 cm in men and < 23.3 cm in women) or Decreased subscapular skinfold thickness (< 7 mm in men and < 7 mm in women) or dual energy X-ray absorptiometry (DEXA) scanning suggestive of fat depletion: total body fat < 14% in men and < 22% in women.
Who cannot join
- History of impaired glucose metabolism or hyperlipidemia prior to antiretroviral use
- Triglyceride levels higher than 1500 mg/dl after the 1 month run-in phase or anytime during the study
- Abnormal hepatic function: liver function tests higher than twice the upper normal range
- Abnormal renal function: creatinine higher than 1.3 mg/dl
- Any condition/illness that may affect study outcomes such as pregnancy, active infection except HIV, clinically significant malabsorption/malnutrition, malignancy
- Any active hormonal disease and/or hormonal treatment that may affect the outcomes of interest such as clinically overt hypo/hyperthyroidism, hypogonadism, hypercortisolism, or treatment with steroids or growth hormone (exception: patients taking testosterone can be included in the trial if they agree to continue the same dosage for the duration of the trial)
- Present alcoholism or drug abuse. These conditions will be screened for by a detailed history and systems review and baseline laboratory analysis with chemistries, CBC, and hormone levels, and EKG.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: A Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome: A Randomized, Double-blind, Placebo-controlled Clinical Trial
The purpose of this study is to determine whether patients with HIV lipodystrophy (fat wasting) benefit from taking the combination of two drugs, one insulin sensitizer (either metformin or pioglitazone, both diabetes drugs) and leptin (a natural hormone produced by your fat cells). Our hope is that they will improve sugar and fat metabolism and positively affect the body fat changes you have noticed while taking HAART.
Read the detailed description
Highly active antiretroviral therapy (HAART) induces profound and sustained suppression of human immunodeficiency virus (HIV) replication, and is thus very effective in reducing disease-associated morbidity and mortality in this patient population. However, HAART also results in the development of a lipodystrophic syndrome which is characterized by fat accumulation, fat wasting, or a combination of both, and similar to congenital forms of lipodystrophy, is associated with components of the metabolic syndrome, including insulin resistance (IR), fasting hypertriglyceridemia, and hypercholesterolemia.
Our study is a "proof of concept" study on the treatment of the HAART-induced metabolic syndrome, which builds upon and represents a direct extension of a study previously funded by the American Diabetes Association (ADA). If our clinical trial proves that a combination treatment of leptin and an insulin sensitizer has additive or synergistic effects in reversing the metabolic abnormalities of HIV positive patients with lipoatrophy, it could lead to the design of larger multi-center, randomized, placebo-controlled trial(s) aiming at establishing safety and efficacy of this treatment for the HAART-induced metabolic syndrome.
- Conditions
- HIV Lipodystrophy
- Being tested
- Leptin, Pioglitazone or metformin, Placebo
- Keywords
- HIV lipodystrophy, Leptin, Fat wasting, Pioglitazone, Insulin resistance
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeptinDrug
Pioglitazone or metforminDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Leptin | Experimental | Leptin replacement therapy Receives: Drug: Leptin; Drug: Pioglitazone or metformin |
| Pioglitazone or metformin | Placebo comparator | Diabetes treatment therapy Receives: Drug: Pioglitazone or metformin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Resistance (HOMA Index)
Measured: At the end of each 3 month intervention
Secondary outcomes (2)
Cholesterol Levels
Measured: At the end of each 3 month intervention
Body Composition (Fat Mass)
Measured: At the end of each 3 month intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2006 (estimated)
- Study startAug 2006
- Primary completionMay 2011
- Study completionJun 2011
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 (1)Papers the sponsor has linked to this study.
- Other trials for HIV LipodystrophyStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Principal investigator, Christos Mantzoros, Beth Israel Deaconess Medical Center
- Investigators
- Christos Mantzoros, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00362440
- Sponsor's protocol ID
- 2005P000159
- Status last verified
- Feb 2017
- First submitted
- 9 Aug 2006
- Last updated
- 23 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab. 2006 Jul;91(7):2605-11. doi: 10.1210/jc.2005-1545. Epub 2006 Apr 24.
PubMed 16636130
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome: A Randomized, Double-blind, Placebo-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT00362440
- Acronym / sponsor ID
- 2005P000159
- Conditions
- HIV Lipodystrophy
- Keywords
- HIV lipodystrophy, Leptin, Fat wasting, Pioglitazone, Insulin resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- American Diabetes Association
- Study start
- Aug 2006
- Primary completion
- May 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 10 Aug 2006 (estimated)
- Results
- Posted 23 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether patients with HIV lipodystrophy (fat wasting) benefit from taking the combination of two drugs, one insulin sensitizer (either metformin or pioglitazone, both diabetes drugs) and leptin (a natural hormone produced by your fat cells). Our hope is that they will improve sugar and fat metabolism and positively affect the body fat changes you have noticed while taking HAART.
Detailed description
Highly active antiretroviral therapy (HAART) induces profound and sustained suppression of human immunodeficiency virus (HIV) replication, and is thus very effective in reducing disease-associated morbidity and mortality in this patient population. However, HAART also results in the development of a lipodystrophic syndrome which is characterized by fat accumulation, fat wasting, or a combination of both, and similar to congenital forms of lipodystrophy, is associated with components of the metabolic syndrome, including insulin resistance (IR), fasting hypertriglyceridemia, and hypercholesterolemia.
Our study is a "proof of concept" study on the treatment of the HAART-induced metabolic syndrome, which builds upon and represents a direct extension of a study previously funded by the American Diabetes Association (ADA). If our clinical trial proves that a combination treatment of leptin and an insulin sensitizer has additive or synergistic effects in reversing the metabolic abnormalities of HIV positive patients with lipoatrophy, it could lead to the design of larger multi-center, randomized, placebo-controlled trial(s) aiming at establishing safety and efficacy of this treatment for the HAART-induced metabolic syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Leptin | Experimental | Drug: Leptin, Drug: Pioglitazone or metforminLeptin replacement therapy |
| Pioglitazone or metformin | Placebo comparator | Drug: Pioglitazone or metformin, Drug: PlaceboDiabetes treatment therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age18 years and above and ability and willingness to give written informed consent
- Documented HIV-1 infection
- At least 6 months of stable cumulative antiretroviral therapy with any available or investigational anti- retroviral medication (protease inhibitor, nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, nucleotide reverse transcriptase inhibitor)
- Lipoatrophy developed after initiating HAART treatment (see criteria below). Leptin levels should be less than 4 ng/ml.
- Insulin resistance, impaired fasting glucose, impaired glucose tolerance or type 2 diabetes developed after starting the antiretroviral medications. These categories are defined, respectively, as fasting insulin level above 15 µIU/ml; fasting serum glucose value above 100 mg/dl; 2-hour serum glucose level during a 75 gram oral glucose tolerance test (OGTT) between 140 and 200 mg/dl; and fasting glucose above 126 mg/dl or random glucose level above 200 mg/dl with presence of the classic symptoms of diabetes, such as polyuria, polydipsia, ketonuria, and rapid weight loss
Key exclusion criteria (7 listed)
- History of impaired glucose metabolism or hyperlipidemia prior to antiretroviral use
- Triglyceride levels higher than 1500 mg/dl after the 1 month run-in phase or anytime during the study
- Abnormal hepatic function: liver function tests higher than twice the upper normal range
- Abnormal renal function: creatinine higher than 1.3 mg/dl
- Any condition/illness that may affect study outcomes such as pregnancy, active infection except HIV, clinically significant malabsorption/malnutrition, malignancy
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 |
|---|---|---|
| Leptin | Drug | Leptin |
| Pioglitazone or metformin | Drug | Leptin, Pioglitazone or metformin |
| Placebo | Drug | Pioglitazone or metformin |
Primary outcome
Insulin Resistance (HOMA Index)
Time frame: At the end of each 3 month intervention
2 secondary outcomes
Cholesterol Levels
Time frame: At the end of each 3 month intervention
Body Composition (Fat Mass)
Time frame: At the end of each 3 month intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16636130Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab. 2006 Jul;91(7):2605-11. doi: 10.1210/jc.2005-1545. Epub 2006 Apr 24.
Related trials for HIV Lipodystrophy
RecruitingObservational study
The LD Lync Study - Natural History Study of Lipodystrophy Syndromes
Lipodystrophy (Genetic or Acquired, Non HIV)
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.
Christos Mantzoros, MD principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leptin and Pioglitazone or metformin in people with HIV Lipodystrophy, run by Beth Israel Deaconess Medical Center at 1 site in United States.
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 10 inclusion and 7 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 23 Mar 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. 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 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 23 Mar 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?
Insulin Resistance (HOMA Index) (time frame: At the end of each 3 month intervention). 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 NCT00362440, which also lists 1 linked publication.
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 23 Mar 2017.