LipodystrophyPhase 2NCT01778556
Short-term Effects of Leptin in People With Lipodystrophy
A Phase 2 study testing Metreleptin in people with Lipodystrophy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Read more about this study
- Who is it for?
- Ages 14 to 70 years
- Conditions the study is for
- Lipodystrophy
- What is being tested?
- Metreleptin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jan 2013to 23 Feb 2018
- 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 14 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 14-70 years (children under age 18 will only be enrolled in the leptin-naive arm of the study
- Clinically-significant lipodystrophy as defined in protocol 02-DK-0022 (Long Term Efficacy of Leptin Replacement in the Treatment of Lipodystrophy). Relevant inclusion criteria for enrollment in protocol 02-DK-0022 are (summarized):
- Lipodystrophy identified by the study physician during physical examination as an absence of fat outside the range of normal
- Circulating leptin levels < 12.0 ng/mL in females and < 8.0 ng/mL in males
- Presence of at least one of the following metabolic abnormalities:
- Diabetes as defined by the 2007 American Diabetes Association criteria
Show all 12Show fewer
- Fasting insulin >30 microU/mL
- Fasting hypertriglyceridemia >200 mg/dL
- Co-enrolled in protocol 02-DK-0022 and either:
- Leptin naive, with plans to initiate leptin treatment during the current study. For the purpose of this study, leptin naive will be defined as having received no exogenous leptin in the 4 months prior to study participation. Thus, subjects who previously received leptin therapy, discontinued, and wish to restart are eligible.
- Or
- --Leptin treated, meaning the subject has taken a stable dose of exogenous leptin for a minimum of 4 months (adults over age 18, only)
Who cannot join
- In leptin treated subjects only, the following exclusion criteria apply:
- Poorly controlled diabetes at study entry (hemoglobin A1c greater than or equal to 9%)
- Poorly controlled hypertriglyceridemia at study entry (serum triglycerides > 800 mg/dL)
- Extreme hypertriglyceridemia prior to leptin (triglycerides greater than 2000 mg/dL at initiation of leptin treatment)
- History of chronic or recurrent acute pancreatitis (> 1 episode), or a single episode of pancreatitis while receiving leptin treatment
- Lipase greater than the upper limit of normal (491 units/L) at study entry
Show all 17Show fewer
- In all subjects (leptin treated and leptin naive), the following exclusion criteria apply:
- Known HIV infection or HIV-associated lipodystrophy
- History of diabetic ketoacidosis
- Active inflammatory disease (e.g. dermatomyositis)
- Change in diabetes or lipid-lowering medications within the past 6 weeks
- Estimated glomerular filtration rate < 30 mL/minute
- Current or recent (past 2 weeks) use of systemic glucocorticoids
- Inadequately controlled hypothyroidism (TSH < 0.4 or >4 mcIU/L) or change in thyroid medication in the past 8 weeks.
- Pregnancy or breast-feeding
- Psychiatric disorder impeding competence or compliance
- Any medical condition or medication that will increase risk to the subject (e.g. ischemic heart disease, decompensated liver disease) or that will interfere with interpretation of study data (e.g. Cushing s syndrome).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Short Term Effects of Leptin Withdrawal or Initiation in Lipodystrophy Independent of Energy Intake
Background:
- Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Leptin helps control appetite and how the body stores food. Taking leptin can help people with lipodystrophy eat less food, which may help treat diabetes and other problems. To better understand how leptin works, researchers want to do an inpatient study on leptin treatment in people with lipodystrophy.
Read more
Objectives:
- To study how leptin treatment affects lipodystrophy.
Eligibility:
- Individuals between 14 and 70 years of age who have lipodystrophy.
Design:
- All participants will have a 19-day stay at the National Institutes of Health Clinical Center. One group of participants will have tests for 5 days before starting to take leptin. They will then take leptin for 2 weeks, and have more tests. The other group of participants will have tests for 5 days while taking leptin. They will then take stop taking leptin for 2 weeks, and have more tests, and then they will start taking leptin again.
- Participants will have regular blood and urine tests during the visit. Some of the blood tests will look at insulin levels. Some will look at how the body metabolizes sugar and fat. Other tests will check hormone levels, especially of reproductive hormones.
- During the visit, participants will spend 3 separate days in a metabolic chamber, a special room that measures how many calories the body uses. Urine samples will be collected during these stays.
- Participants will also have several body imaging studies, including magnetic resonance imaging and a body composition scan.
- Physical activity will be tested with an exercise bicycle and an electronic activity monitor.
- Participants will be asked questions about hunger and comfort levels throughout the stay.
Read the detailed description
Background
Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue to the rest of the body conveying information about long-term nutritional status. Patients with lipodystrophy have leptin deficiency secondary to lack of adipose tissue, and thus represent a natural model for studying the effects of leptin deficiency and replacement in humans. Leptin replacement in lipodystrophy ameliorates metabolic and endocrine abnormalities, including reducing food intake, improving insulin resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. The reduction in energy intake induced by leptin replacement is likely responsible for part of the improvements observed in glucose and lipid metabolism. The clinical effects of leptin that are independent of changes in energy intake, and the mechanisms underlying these effects, have been poorly explored in humans.
Aim
The primary aim of this study is to determine the energy intake-independent effects of leptin on energy metabolism in lipodystrophic subjects. The major aspects of energy metabolism to be studied are:
- Lipid metabolism, including fasting lipids, lipolysis and fatty acid turnover, and ectopic lipid storage.
- Glucose metabolism, including fasting glucose, endogenous glucose production, and insulin sensitivity
- Energy expenditure, including total and resting energy expenditure, skeletal muscle work efficiency, and spontaneous physical activity
In addition, the effects of leptin on endocrine and autonomic function will be examined, including effects on the thyroid, gonadal, and adrenal axes, as well as blood pressure, body temperature, and heart rate variability.
Methods
This is a non-randomized, parallel group study. Two groups of patients aged 14 to 70 years with lipodystrophy will be studied: leptin naive and leptin treated. Minors will only be included in the leptin naive arm. All subjects will be stabilized on a weight maintenance diet for 5 days (Period 1). After this, leptin will be withdrawn from leptin treated subjects, and leptin will be initiated in leptin naive subjects for a period of 14 days (Period 2). The same isocaloric diet will be continued throughout both Periods, permitting study of leptin s effects independent of energy intake.
All subjects will undergo metabolic testing on admission, at the end of Period 1, and throughout Period 2, to generate a detailed short-term time course of the effects of leptin initiation or withdrawal. At the end of Period 2, leptin will be continued in the leptin naive subjects, and restarted in the leptin treated subjects. Repeat metabolic testing will be performed 6-12 months after leptin initiation in the leptin-naive cohort to generate information on leptin s long-term effects.
- Conditions
- Lipodystrophy
- Being tested
- Metreleptin
- Keywords
- Lipodystrophy, Leptin, Energy Expenditure, Diabetes, Hypertriglyceridemia
- Medical subject headings
- Lipodystrophy, Diabetes Mellitus, Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetreleptinBiological
Recombinant analog of the human hormone, leptin
| Study group | Role | What they receive |
|---|---|---|
| Leptin naive | Experimental | Studied for 5 days without metreleptin, then 14 days while taking metreleptin Receives: Biological: Metreleptin |
| On-leptin | Experimental | Studied for 5 days while taking metreleptin, then 14 days during metreleptin withdrawal Receives: Biological: Metreleptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Body Insulin Sensitivity
Total body insulin sensitivity (measured as glucose disposal rate during a hyperinsulinemic, euglycemic clamp)
Measured: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Secondary outcomes (2)
Insulin-mediated Suppression of Hepatic Glucose Production
Hepatic insulin sensitivity (measured as suppression of endogenous glucose production during a hyperinsulinemic, euglycemic clamp)
Measured: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Endogenous Rate of Appearance of Palmitate
Endogenous Rate of Appearance of Palmitate is measured in plasma.
Measured: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study start26 Jan 2013
- Primary completion23 Feb 2018
- Study completion23 Feb 2018
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 (12)Papers the sponsor has linked to this study.
- Other trials for LipodystrophyStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rebecca J Brown, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01778556
- Sponsor's protocol ID
- 130057
- Other IDs
- 13-DK-0057
- Status last verified
- 25 Feb 2019
- First submitted
- 26 Jan 2013
- Last updated
- 13 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
Publications
Ahima RS, Dushay J, Flier SN, Prabakaran D, Flier JS. Leptin accelerates the onset of puberty in normal female mice. J Clin Invest. 1997 Feb 1;99(3):391-5. doi: 10.1172/JCI119172.
PubMed 9022071Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul 18;382(6588):250-2. doi: 10.1038/382250a0.
PubMed 8717038Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996 Mar;12(3):318-20. doi: 10.1038/ng0396-318.
PubMed 8589726Quaye E, Chacko S, Startzell M, Brown RJ. Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e209-e215. doi: 10.1210/clinem/dgad445.
PubMed 37515588Meral R, Malandrino N, Walter M, Neidert AH, Muniyappa R, Oral EA, Brown RJ. Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1739-e1751. doi: 10.1210/clinem/dgab760.
PubMed 34677608Nguyen ML, Sachdev V, Burklow TR, Li W, Startzell M, Auh S, Brown RJ. Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4327-e4339. doi: 10.1210/clinem/dgab499.
PubMed 34223895Grover A, Quaye E, Brychta RJ, Christensen J, Startzell MS, Meehan CA, Valencia A, Marshall B, Chen KY, Brown RJ. Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4163-e4178. doi: 10.1210/clinem/dgab269.
PubMed 33890058Baykal AP, Parks EJ, Shamburek R, Syed-Abdul MM, Chacko S, Cochran E, Startzell M, Gharib AM, Ouwerkerk R, Abd-Elmoniem KZ, Walter PJ, Walter M, Muniyappa R, Chung ST, Brown RJ. Leptin decreases de novo lipogenesis in patients with lipodystrophy. JCI Insight. 2020 Jul 23;5(14):e137180. doi: 10.1172/jci.insight.137180.
PubMed 32573497Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
PubMed 32191645Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of Metreleptin Treatment in Familial Partial Lipodystrophy Due to PPARG vs LMNA Pathogenic Variants. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3068-3076. doi: 10.1210/jc.2018-02787.
PubMed 31194872Brown RJ, Valencia A, Startzell M, Cochran E, Walter PJ, Garraffo HM, Cai H, Gharib AM, Ouwerkerk R, Courville AB, Bernstein S, Brychta RJ, Chen KY, Walter M, Auh S, Gorden P. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy. J Clin Invest. 2018 Aug 1;128(8):3504-3516. doi: 10.1172/JCI95476. Epub 2018 Jul 16.
PubMed 29723161Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P. Effects of Metreleptin in Pediatric Patients With Lipodystrophy. J Clin Endocrinol Metab. 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628.
PubMed 28324110
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Term Effects of Leptin Withdrawal or Initiation in Lipodystrophy Independent of Energy Intake
- ClinicalTrials.gov ID
- NCT01778556
- Acronym / sponsor ID
- 130057
- Conditions
- Lipodystrophy
- Keywords
- Lipodystrophy, Leptin, Energy Expenditure, Diabetes, Hypertriglyceridemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 26 Jan 2013
- Primary completion
- 23 Feb 2018 (actual)
- Study completion
- 23 Feb 2018 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Posted 13 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Leptin helps control appetite and how the body stores food. Taking leptin can help people with lipodystrophy eat less food, which may help treat diabetes and other problems. To better understand how leptin works, researchers want to do an inpatient study on leptin treatment in people with lipodystrophy.
Objectives:
- To study how leptin treatment affects lipodystrophy.
Eligibility:
- Individuals between 14 and 70 years of age who have lipodystrophy.
Design:
- All participants will have a 19-day stay at the National Institutes of Health Clinical Center. One group of participants will have tests for 5 days before starting to take leptin. They will then take leptin for 2 weeks, and have more tests. The other group of participants will have tests for 5 days while taking leptin. They will then take stop taking leptin for 2 weeks, and have more tests, and then they will start taking leptin again.
- Participants will have regular blood and urine tests during the visit. Some of the blood tests will look at insulin levels. Some will look at how the body metabolizes sugar and fat. Other tests will check hormone levels, especially of reproductive hormones.
- During the visit, participants will spend 3 separate days in a metabolic chamber, a special room that measures how many calories the body uses. Urine samples will be collected during these stays.
- Participants will also have several body imaging studies, including magnetic resonance imaging and a body composition scan.
- Physical activity will be tested with an exercise bicycle and an electronic activity monitor.
- Participants will be asked questions about hunger and comfort levels throughout the stay.
Detailed description
Background
Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue to the rest of the body conveying information about long-term nutritional status. Patients with lipodystrophy have leptin deficiency secondary to lack of adipose tissue, and thus represent a natural model for studying the effects of leptin deficiency and replacement in humans. Leptin replacement in lipodystrophy ameliorates metabolic and endocrine abnormalities, including reducing food intake, improving insulin resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. The reduction in energy intake induced by leptin replacement is likely responsible for part of the improvements observed in glucose and lipid metabolism. The clinical effects of leptin that are independent of changes in energy intake, and the mechanisms underlying these effects, have been poorly explored in humans.
Aim
The primary aim of this study is to determine the energy intake-independent effects of leptin on energy metabolism in lipodystrophic subjects. The major aspects of energy metabolism to be studied are:
- Lipid metabolism, including fasting lipids, lipolysis and fatty acid turnover, and ectopic lipid storage.
- Glucose metabolism, including fasting glucose, endogenous glucose production, and insulin sensitivity
- Energy expenditure, including total and resting energy expenditure, skeletal muscle work efficiency, and spontaneous physical activity
In addition, the effects of leptin on endocrine and autonomic function will be examined, including effects on the thyroid, gonadal, and adrenal axes, as well as blood pressure, body temperature, and heart rate variability.
Methods
This is a non-randomized, parallel group study. Two groups of patients aged 14 to 70 years with lipodystrophy will be studied: leptin naive and leptin treated. Minors will only be included in the leptin naive arm. All subjects will be stabilized on a weight maintenance diet for 5 days (Period 1). After this, leptin will be withdrawn from leptin treated subjects, and leptin will be initiated in leptin naive subjects for a period of 14 days (Period 2). The same isocaloric diet will be continued throughout both Periods, permitting study of leptin s effects independent of energy intake.
All subjects will undergo metabolic testing on admission, at the end of Period 1, and throughout Period 2, to generate a detailed short-term time course of the effects of leptin initiation or withdrawal. At the end of Period 2, leptin will be continued in the leptin naive subjects, and restarted in the leptin treated subjects. Repeat metabolic testing will be performed 6-12 months after leptin initiation in the leptin-naive cohort to generate information on leptin s long-term effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Leptin naive | Experimental | Biological: MetreleptinStudied for 5 days without metreleptin, then 14 days while taking metreleptin |
| On-leptin | Experimental | Biological: MetreleptinStudied for 5 days while taking metreleptin, then 14 days during metreleptin withdrawal |
Who may qualify
- Ages
- 14 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Age 14-70 years (children under age 18 will only be enrolled in the leptin-naive arm of the study
- Clinically-significant lipodystrophy as defined in protocol 02-DK-0022 (Long Term Efficacy of Leptin Replacement in the Treatment of Lipodystrophy). Relevant inclusion criteria for enrollment in protocol 02-DK-0022 are (summarized):
- Co-enrolled in protocol 02-DK-0022 and either:
- Or
- --Leptin treated, meaning the subject has taken a stable dose of exogenous leptin for a minimum of 4 months (adults over age 18, only)
Key exclusion criteria (17 listed)
- Poorly controlled diabetes at study entry (hemoglobin A1c greater than or equal to 9%)
- Poorly controlled hypertriglyceridemia at study entry (serum triglycerides > 800 mg/dL)
- Extreme hypertriglyceridemia prior to leptin (triglycerides greater than 2000 mg/dL at initiation of leptin treatment)
- History of chronic or recurrent acute pancreatitis (> 1 episode), or a single episode of pancreatitis while receiving leptin treatment
- Lipase greater than the upper limit of normal (491 units/L) at 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 |
|---|---|---|
| MetreleptinRecombinant analog of the human hormone, leptin | Biological | Leptin naive, On-leptin |
Primary outcome
Total Body Insulin Sensitivity
Time frame: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Total body insulin sensitivity (measured as glucose disposal rate during a hyperinsulinemic, euglycemic clamp)
2 secondary outcomes
Insulin-mediated Suppression of Hepatic Glucose Production
Time frame: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Endogenous Rate of Appearance of Palmitate
Time frame: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9022071Ahima RS, Dushay J, Flier SN, Prabakaran D, Flier JS. Leptin accelerates the onset of puberty in normal female mice. J Clin Invest. 1997 Feb 1;99(3):391-5. doi: 10.1172/JCI119172.
- Background: PubMed 8717038Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul 18;382(6588):250-2. doi: 10.1038/382250a0.
- Background: PubMed 8589726Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996 Mar;12(3):318-20. doi: 10.1038/ng0396-318.
- Derived from this study: PubMed 37515588Quaye E, Chacko S, Startzell M, Brown RJ. Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e209-e215. doi: 10.1210/clinem/dgad445.
- Derived from this study: PubMed 34677608Meral R, Malandrino N, Walter M, Neidert AH, Muniyappa R, Oral EA, Brown RJ. Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1739-e1751. doi: 10.1210/clinem/dgab760.
- Derived from this study: PubMed 34223895Nguyen ML, Sachdev V, Burklow TR, Li W, Startzell M, Auh S, Brown RJ. Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4327-e4339. doi: 10.1210/clinem/dgab499.
- Derived from this study: PubMed 33890058Grover A, Quaye E, Brychta RJ, Christensen J, Startzell MS, Meehan CA, Valencia A, Marshall B, Chen KY, Brown RJ. Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4163-e4178. doi: 10.1210/clinem/dgab269.
- Derived from this study: PubMed 32573497Baykal AP, Parks EJ, Shamburek R, Syed-Abdul MM, Chacko S, Cochran E, Startzell M, Gharib AM, Ouwerkerk R, Abd-Elmoniem KZ, Walter PJ, Walter M, Muniyappa R, Chung ST, Brown RJ. Leptin decreases de novo lipogenesis in patients with lipodystrophy. JCI Insight. 2020 Jul 23;5(14):e137180. doi: 10.1172/jci.insight.137180.
- Derived from this study: PubMed 32191645Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
- Derived from this study: PubMed 31194872Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of Metreleptin Treatment in Familial Partial Lipodystrophy Due to PPARG vs LMNA Pathogenic Variants. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3068-3076. doi: 10.1210/jc.2018-02787.
- Derived from this study: PubMed 29723161Brown RJ, Valencia A, Startzell M, Cochran E, Walter PJ, Garraffo HM, Cai H, Gharib AM, Ouwerkerk R, Courville AB, Bernstein S, Brychta RJ, Chen KY, Walter M, Auh S, Gorden P. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy. J Clin Invest. 2018 Aug 1;128(8):3504-3516. doi: 10.1172/JCI95476. Epub 2018 Jul 16.
- Derived from this study: PubMed 28324110Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P. Effects of Metreleptin in Pediatric Patients With Lipodystrophy. J Clin Endocrinol Metab. 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Rebecca J Brown, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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 Metreleptin in people with Lipodystrophy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 12 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 13 Nov 2019. 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 13 Nov 2019). 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?
Total Body Insulin Sensitivity (time frame: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)). 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 NCT01778556, which also lists 12 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 13 Nov 2019.