HIV LipodystrophyNCT01511016
Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome
A study testing Human recombinant leptin ("metreleptin") in people with HIV Lipodystrophy, run by Baylor College of Medicine at 1 site in United States.
Trial summary
"HIV lipodystrophy syndrome" (HLS) is characterized by loss of fat in the arms and legs, with increase in fat in the abdomen, and abnormal blood lipid levels. Persons with HLS have high risk for cardiovascular disease and diabetes mellitus and the metabolic syndrome. Read more about this study
- Who is it for?
- Ages 18 to 64 years, men only
- Conditions the study is for
- HIV Lipodystrophy
- What is being tested?
- Human recombinant leptin ("metreleptin")
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Oct 2011
- Phase
- Interventional
- 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 to 64 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- predominantly lipoatrophic or mixed phenotype of HIV-lipodystrophy (based on self-observation and evaluation by a study physician utilizing a visual scale;
- AM fasting leptin < 4.0 ng/ml
- hypertriglyceridemia (fasting serum TG 250-1000 mg /dl).
- normal biochemistry (except altered lipid and glucose profile). Patients with the American Diabetes Association diagnostic criteria for diabetes were included provided the HbA1c level was <7.5% and they received no anti-diabetic medications for at least 3 months.
- well-controlled HIV infection status evidenced by viral RNA titers <400 copies/ml, on stable HAART.
Who cannot join
- acute or chronic illnesses.
- use of antidiabetic medications in the previous 3 months, or of lipid-lowering drugs in the previous 6 weeks are also exclusion criteria. Other drugs excluded are growth hormone (if used without evidence of growth hormone deficiency), Megace and testosterone (if used without evidence of hypogonadism).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Leptin Therapy on Abnormal Lipid Kinetics in Subjects With HIV Lipodystrophy Syndrome
"HIV lipodystrophy syndrome" (HLS) is characterized by loss of fat in the arms and legs, with increase in fat in the abdomen, and abnormal blood lipid levels. Persons with HLS have high risk for cardiovascular disease and diabetes mellitus and the metabolic syndrome. The investigators have previously shown that the abnormal lipid levels and lipodystrophy in HLS are associated with defective regulation of lipid metabolic rates, specifically, accelerated lipolysis (breakdown of stored fats), and decreased fat oxidation (utilization of fats for energy). Patients with HLS also have low levels of the hormone leptin. The investigators hypothesize that treatment of these patients with leptin will improve fat oxidation and may slow the rate of lipolysis. Hence, the investigators propose to study the effect of leptin therapy on lipid metabolic rates and lipid and glucose levels in adults with HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure lipolysis, fat oxidation, and fat re-esterification in adipose tissues and liver.
Read the detailed description
The HIV lipodystrophy syndrome (HLS) is characterized by peripheral fat wasting and central obesity, and hyperlipidemia (mainly hypertriglyceridemia), which results in insulin resistance. HLS patients are at high risk for cardiovascular disease, diabetes mellitus and the metabolic syndrome.
The investigators have previously shown that the alterations in lipid metabolism in the so-called mixed form of HLS are due to dysregulation of lipid kinetics at two levels. First, there appears to be an acceleration in lipid kinetics, with higher total and net lipolysis despite higher intra-adipocyte re-esterification. However, the percentage of fatty acid flux being oxidized remains the same, leading to increased hepatic recycling of fatty acids to triglycerides (TG), and export of TG-rich VLDL into the circulation. Second, there is reduced clearance of chylomicron and VLDL-TG from the plasma, resulting in the striking hypertriglyceridemia associated with this syndrome. The investigators propose that these alterations in lipid kinetics account for the phenotypic changes characteristic of this syndrome: increased lipolysis would facilitate peripheral lipoatrophy, increased intra-adipocyte re-esterification (if selective in intrabdominal depots) would contribute to the central obesity, and increased hepatic re-esterification together with impaired VLDL- and chylomicron-TG clearance would lead to hypertriglyceridemia.
Rational treatment of HLS should be targeted at these fundamental kinetic defects. Leptin is in many ways an ideal agent, since it increases fat oxidation, and shifts the ratio of utilization of free fatty acids derived from lipolysis towards oxidation and away from re-esterification, and decreases plasma triglyceride levels. HLS patients with lipoatrophy have low circulating levels of leptin. Moreover, leptin has been shown to be effective in correcting similar defects in fat redistribution and circulating lipids in non-HIV forms of lipodystrophy. Hence, the investigators propose to study (using a blinded, placebo-controlled, dose escalating design) the effect of leptin therapy on lipid kinetics and fat distribution in adult subjects with the lipoatrophic and mixed (peripheral lipoatrophy and central adiposity) forms of HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure whole body lipolysis, lipid oxidation, lipid re-esterification and hepatic lipid recycling.
- Conditions
- HIV Lipodystrophy
- Being tested
- Human recombinant leptin ("metreleptin"), Placebo
- Keywords
- lipid kinetics, fat oxidation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human recombinant leptin ("metreleptin")Drug
Also called metreleptin
Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
PlaceboDrug
Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.
| Study group | Role | What they receive |
|---|---|---|
| human recombinant leptin (metreleptin) | Experimental | Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Receives: Drug: Human recombinant leptin ("metreleptin") |
| Placebo injection | Placebo comparator | Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Total Lipolysis
Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
Measured: 4 months after treatment
Rate of Net Lipolysis
Rate of net lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
Measured: 4 months after treatment
Secondary outcomes (4)
Rates of Fatty Acid Oxidation
Rates of fatty acid oxidation were measured in breath samples following stable isotope infusions of 13C-labeled palmitate.
Measured: 4 months after treatment
Fasting Plasma Non-HDL-C
Fasting plasma non-HDL-cholesterol was calculated from measured total cholesterol and HDL cholesterol.
Measured: 4 months after treatment.
Glucose Levels After Glucose Challenge
An oral glucose tolerance test was performed. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a standard clinical test of glucose tolerance. i.e., a test for diabetes and pre-diabetes. Although multiple time points are used in this test, the outcome is a single value, either a blood glucose level after 2 hours or an area-under-the-curve. In this study we are reporting the area-under-the-curve.
Measured: 4 months after treatment.
Insulin Levels After Oral Glucose Challenge.
An oral glucose tolerance test was performed to measure endogenous insulin response. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a clinical test of endogenous insulin response to glucose i.e., an endocrine test. Although multiple time points are used in this test, the outcome is a single value, i.e., an area-under-the-curve for insulin.
Measured: 4 months after treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2012 (estimated)
- Study startFeb 2003
- Primary completionJun 2011
- Study completionOct 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 Baylor College of MedicineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ashok Balasubramanyam, Baylor College of Medicine
- Investigators
- Ashok Balasubramanyam, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01511016
- Sponsor's protocol ID
- H-13372
- Status last verified
- Dec 2015
- First submitted
- 11 Jan 2012
- Last updated
- 27 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sekhar RV, Jahoor F, Iyer D, Guthikonda A, Paranilam J, Elhaj F, Coraza I, Balasubramanyam A. Leptin replacement therapy does not improve the abnormal lipid kinetics of hypoleptinemic patients with HIV-associated lipodystrophy syndrome. Metabolism. 2012 Oct;61(10):1395-403. doi: 10.1016/j.metabol.2012.03.013. Epub 2012 Apr 28.
PubMed 22542724
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Leptin Therapy on Abnormal Lipid Kinetics in Subjects With HIV Lipodystrophy Syndrome
- ClinicalTrials.gov ID
- NCT01511016
- Acronym / sponsor ID
- H-13372
- Conditions
- HIV Lipodystrophy
- Keywords
- lipid kinetics, fat oxidation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Feb 2003
- Primary completion
- Jun 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 18 Jan 2012 (estimated)
- Results
- Posted 27 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
"HIV lipodystrophy syndrome" (HLS) is characterized by loss of fat in the arms and legs, with increase in fat in the abdomen, and abnormal blood lipid levels. Persons with HLS have high risk for cardiovascular disease and diabetes mellitus and the metabolic syndrome. The investigators have previously shown that the abnormal lipid levels and lipodystrophy in HLS are associated with defective regulation of lipid metabolic rates, specifically, accelerated lipolysis (breakdown of stored fats), and decreased fat oxidation (utilization of fats for energy). Patients with HLS also have low levels of the hormone leptin. The investigators hypothesize that treatment of these patients with leptin will improve fat oxidation and may slow the rate of lipolysis. Hence, the investigators propose to study the effect of leptin therapy on lipid metabolic rates and lipid and glucose levels in adults with HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure lipolysis, fat oxidation, and fat re-esterification in adipose tissues and liver.
Detailed description
The HIV lipodystrophy syndrome (HLS) is characterized by peripheral fat wasting and central obesity, and hyperlipidemia (mainly hypertriglyceridemia), which results in insulin resistance. HLS patients are at high risk for cardiovascular disease, diabetes mellitus and the metabolic syndrome.
The investigators have previously shown that the alterations in lipid metabolism in the so-called mixed form of HLS are due to dysregulation of lipid kinetics at two levels. First, there appears to be an acceleration in lipid kinetics, with higher total and net lipolysis despite higher intra-adipocyte re-esterification. However, the percentage of fatty acid flux being oxidized remains the same, leading to increased hepatic recycling of fatty acids to triglycerides (TG), and export of TG-rich VLDL into the circulation. Second, there is reduced clearance of chylomicron and VLDL-TG from the plasma, resulting in the striking hypertriglyceridemia associated with this syndrome. The investigators propose that these alterations in lipid kinetics account for the phenotypic changes characteristic of this syndrome: increased lipolysis would facilitate peripheral lipoatrophy, increased intra-adipocyte re-esterification (if selective in intrabdominal depots) would contribute to the central obesity, and increased hepatic re-esterification together with impaired VLDL- and chylomicron-TG clearance would lead to hypertriglyceridemia.
Rational treatment of HLS should be targeted at these fundamental kinetic defects. Leptin is in many ways an ideal agent, since it increases fat oxidation, and shifts the ratio of utilization of free fatty acids derived from lipolysis towards oxidation and away from re-esterification, and decreases plasma triglyceride levels. HLS patients with lipoatrophy have low circulating levels of leptin. Moreover, leptin has been shown to be effective in correcting similar defects in fat redistribution and circulating lipids in non-HIV forms of lipodystrophy. Hence, the investigators propose to study (using a blinded, placebo-controlled, dose escalating design) the effect of leptin therapy on lipid kinetics and fat distribution in adult subjects with the lipoatrophic and mixed (peripheral lipoatrophy and central adiposity) forms of HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure whole body lipolysis, lipid oxidation, lipid re-esterification and hepatic lipid recycling.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| human recombinant leptin (metreleptin) | Experimental | Drug: Human recombinant leptin ("metreleptin")Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. |
| Placebo injection | Placebo comparator | Drug: PlaceboEach subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- predominantly lipoatrophic or mixed phenotype of HIV-lipodystrophy (based on self-observation and evaluation by a study physician utilizing a visual scale;
- AM fasting leptin < 4.0 ng/ml
- hypertriglyceridemia (fasting serum TG 250-1000 mg /dl).
- normal biochemistry (except altered lipid and glucose profile). Patients with the American Diabetes Association diagnostic criteria for diabetes were included provided the HbA1c level was <7.5% and they received no anti-diabetic medications for at least 3 months.
- well-controlled HIV infection status evidenced by viral RNA titers <400 copies/ml, on stable HAART.
Key exclusion criteria (2 listed)
- acute or chronic illnesses.
- use of antidiabetic medications in the previous 3 months, or of lipid-lowering drugs in the previous 6 weeks are also exclusion criteria. Other drugs excluded are growth hormone (if used without evidence of growth hormone deficiency), Megace and testosterone (if used without evidence of hypogonadism).
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 |
|---|---|---|
| Human recombinant leptin ("metreleptin")Also: metreleptinMetreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months. | Drug | human recombinant leptin (metreleptin) |
| PlaceboPlacebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months. | Drug | Placebo injection |
Primary outcome
Rate of Total Lipolysis
Time frame: 4 months after treatment
Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
Rate of Net Lipolysis
Time frame: 4 months after treatment
Rate of net lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
4 secondary outcomes
Rates of Fatty Acid Oxidation
Time frame: 4 months after treatment
Fasting Plasma Non-HDL-C
Time frame: 4 months after treatment.
Glucose Levels After Glucose Challenge
Time frame: 4 months after treatment.
Insulin Levels After Oral Glucose Challenge.
Time frame: 4 months after treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22542724Sekhar RV, Jahoor F, Iyer D, Guthikonda A, Paranilam J, Elhaj F, Coraza I, Balasubramanyam A. Leptin replacement therapy does not improve the abnormal lipid kinetics of hypoleptinemic patients with HIV-associated lipodystrophy syndrome. Metabolism. 2012 Oct;61(10):1395-403. doi: 10.1016/j.metabol.2012.03.013. Epub 2012 Apr 28.
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.
Ashok Balasubramanyam, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Human recombinant leptin ("metreleptin") in people with HIV Lipodystrophy, run by Baylor College of Medicine 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 5 inclusion and 2 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 27 Jan 2016. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2016). 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?
Rate of Total Lipolysis (time frame: 4 months after treatment). 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 NCT01511016, 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 27 Jan 2016.