LipodystrophyPhase 2NCT00005905
Leptin to Treat Lipodystrophy
A Phase 2 study testing hu Leptin (A-100) in people with Lipodystrophy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of the leptin replacement therapy in treating lipoatrophy or lipodystrophy-a condition in which there is a total or partial loss of fat cells. Patients with lipodystrophy lack sufficient leptin, because this hormone is produced by fat cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lipodystrophy
- What is being tested?
- hu Leptin (A-100)
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2000to Apr 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All ethnic groups
- Males and females
- Age greater than 14 years
- Clinically-significant lipodystrophy, identified by the study physician during the physical examination as an absence of fat outside the range of normal variation and/or identified as a disfiguring factor by the patient.
- Circulating leptin levels less than 4.0 ng/ml in females and less than 3.0 ng/ml in males as measured by Linco assay on at least 2 occasions.
- Presence of at least one of the following metabolic abnormalities:
Show all 9Show fewer
- Presence of diabetes as defined by the 1997 ADA criteria: a) fasting plasma glucose greater than or equal to 126 mg/dL, or b) 2 hour plasma glucose greater than or equal to 200 mg/dL following a 75 gram oral glucose load, or c) diabetic symptoms with a random plasma glucose greater than or equal to 200 mg/dL.
- Fasting insulin greater than 30 micrograms/ml;
- Fasting hypertriglyceridemia greater than 200 mg/dl.
Who cannot join
- General: Pregnant women, women in their reproductive years who do not use an effective method of birth control, women currently nursing or lactating within 6 weeks of having completed nursing, and persons who are unable to provide informed consent will be excluded from the study.
- Exclusions for underlying disease likely to increase side effects or to hinder objective data collection:
- Known liver disease due to causes other than non-alcoholic steatohepatitis
- Current alcohol or substance abuse
- Psychiatric disorder impeding competence or compliance
- Active tuberculosis
Show all 9Show fewer
- Use of anorexiogenic drugs
- Other condition which in the opinion of the clinical investigators would impede completion of the study
- Subjects who have a known hypersensitivity to E. Coli derived proteins
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Bethesda, Maryland, 20892
About this study
Official title: Efficacy of Leptin Replacement in Treatment of Lipodystrophy
This study will evaluate the safety and effectiveness of the leptin replacement therapy in treating lipoatrophy or lipodystrophy-a condition in which there is a total or partial loss of fat cells. Patients with lipodystrophy lack sufficient leptin, because this hormone is produced by fat cells. The leptin deficiency usually causes high blood lipid (fat) levels and insulin resistance that may lead to diabetes. Patients may have hormone imbalances, fertility problems, uncontrolled appetite, and liver disease due to fat accumulation.
Patients 15 years and older with lipodystrophy are eligible for this study. Candidates are screened with a medical history and physical examination, and fasting blood tests. Those enrolled undergo the following additional procedures:
Read more
- Ultrasound of the liver and, if abnormalities are found, possibly a liver biopsy
- Resting metabolic rate measurement - measures the amount of oxygen breathed at rest in order to calculate how many calories are required to maintain resting body functions
- Magnetic resonance imaging of the liver and other organs, and of muscle and fat
- Estimation of body fat - measurements of height, weight, hip size, and skin folds over the arms and abdomen to estimate body fat content
- Insulin tolerance test - measures blood glucose levels after administration of insulin. Insulin is given through an intravenous (IV) catheter (a thin tube placed in a vein) and blood is drawn 5 minutes before the test begins, when the test begins, and 5, 10, 15, 20 and 30 minutes into the test
- Oral glucose tolerance test - measures blood glucose and insulin levels after drinking a glucose (sugar) solution. Blood samples are drawn through an IV catheter 15 minutes before the test begins, at the time the test begins, and 30, 60, 90 and 180 minutes into the test
- Intravenous glucose tolerance test - measures tissue response to insulin and glucose after glucose is injected into a vein. The glucose injection is followed by a short infusion of insulin and then blood samples are taken over 3 hours to measure insulin and glucose levels
- Appetite level and food intake - measures hunger level and caloric intake. Patients are questioned about their hunger level, given a variety of foods they may choose to eat and questioned again at various intervals about hunger level. On another day, patients are given breakfast (usually a milkshake) and when they want to eat again, the appetite level and caloric intake study is repeated.
- Hormone function tests - the function of three hormones influenced by leptin (corticotropin-releasing hormone, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone) are assessed. The hormones are injected intravenously and then blood samples are drawn.
When all the tests are completed, leptin therapy begins. The drug is injected under the skin twice a day for 4 months by the patient or a caregiver (similar to self-administered insulin injections for diabetes). Blood is drawn once a month to monitor the effects of treatment and drug side effects. At clinic visits scheduled 1, 2 and 4 months after therapy starts, patients have a physical examination and meet with a dietitian. Medication dosage is also increased at these visits. At the end of 4 months, all baseline studies described above are repeated. Throughout the study, all patients complete a form once a week, in which they record their symptoms. Patients with diabetes also measure their blood glucose levels at home before each meal and at bedtime.
Read the detailed description
Lipoatrophic diabetes is a syndrome characterized by insulin resistance in association with a paucity of adipose tissue. Patients with severe lipoatrophy die prematurely, typically from the complications of diabetes or liver disease. Experiments with lipoatrophic mice suggest that the insulin resistance is caused by the lack of adipose tissue. Adipose tissue normally produces leptin, a hormone that increases insulin action. To what extent does leptin deficiency cause diabetes in lipoatrophic patients? In one mouse model of lipoatrophy, leptin administration reversed the diabetes and liver disease. In a different, more severely adipose-deficient mouse, the effects of leptin treatment were detectable, but more modest.
In this protocol, to be carried out at both the NIH and the University of Texas in Dallas, we test the hypotheses that leptin can be safely administered to patients with lipoatrophic diabetes and they will benefit from treatment with A-100 (recombinant form of human leptin provided by Amgen). We will study patients with lipoatrophy, low leptin levels, and at least one of the following metabolic abnormalities: severe insulin resistance, diabetes, and/or hypertriglyceridemia.
We will treat patients with A-100 injections for four months, with inpatient studies at baseline, 1, 2, and 4 months of treatment. In the core protocol, we will monitor metabolic control (e.g. glucose, insulin, free fatty acid, and triglyceride levels). Ancillary studies will evaluate the effect of A-100 on the gonadal axis and on liver pathology.
After 8 months of treatment, we will offer a withdrawal study to the patient requiring an inpatient admission and controlled diet. Afterwards leptin therapy will resume in a long-term extension study with follow up visits every 6 months. Metabolic parameters will continue to be followed, along with body fat imaging studies, gonadotropin monitoring, and liver function analysis.
- Conditions
- Lipodystrophy
- Being tested
- hu Leptin (A-100)
- Keywords
- Adipocyte - Development, Insulin Resistance, Dyslipidemia, Diabetes Mellitus, Non-Alcoholic Steatohepatitis, Leptin Replacement
- Medical subject headings
- Lipodystrophy, Insulin Resistance, Dyslipidemias, Diabetes Mellitus, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hu Leptin (A-100)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2000 (estimated)
- Study startJun 2000
- Study completionApr 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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
- Enrolment
- 20 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005905
- Sponsor's protocol ID
- 000146
- Other IDs
- 00-DK-0146
- Status last verified
- Apr 2003
- First submitted
- 9 Jun 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Burant CF, Sreenan S, Hirano K, Tai TA, Lohmiller J, Lukens J, Davidson NO, Ross S, Graves RA. Troglitazone action is independent of adipose tissue. J Clin Invest. 1997 Dec 1;100(11):2900-8. doi: 10.1172/JCI119839.
PubMed 9389757Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, Feigenbaum L, Lee E, Aoyama T, Eckhaus M, Reitman ML, Vinson C. Life without white fat: a transgenic mouse. Genes Dev. 1998 Oct 15;12(20):3168-81. doi: 10.1101/gad.12.20.3168.
PubMed 9784492Taylor SI, Arioglu E. Syndromes associated with insulin resistance and acanthosis nigricans. J Basic Clin Physiol Pharmacol. 1998;9(2-4):419-39. doi: 10.1515/jbcpp.1998.9.2-4.419. No abstract available.
PubMed 10212846Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ. Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491.
PubMed 37595266Sekizkardes 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, 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 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Leptin Replacement in Treatment of Lipodystrophy
- ClinicalTrials.gov ID
- NCT00005905
- Acronym / sponsor ID
- 000146
- Conditions
- Lipodystrophy
- Keywords
- Adipocyte - Development, Insulin Resistance, Dyslipidemia, Diabetes Mellitus, Non-Alcoholic Steatohepatitis, Leptin Replacement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Jun 2000
- Study completion
- Apr 2003
- First posted
- 12 Jun 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and effectiveness of the leptin replacement therapy in treating lipoatrophy or lipodystrophy-a condition in which there is a total or partial loss of fat cells. Patients with lipodystrophy lack sufficient leptin, because this hormone is produced by fat cells. The leptin deficiency usually causes high blood lipid (fat) levels and insulin resistance that may lead to diabetes. Patients may have hormone imbalances, fertility problems, uncontrolled appetite, and liver disease due to fat accumulation.
Patients 15 years and older with lipodystrophy are eligible for this study. Candidates are screened with a medical history and physical examination, and fasting blood tests. Those enrolled undergo the following additional procedures:
- Ultrasound of the liver and, if abnormalities are found, possibly a liver biopsy
- Resting metabolic rate measurement - measures the amount of oxygen breathed at rest in order to calculate how many calories are required to maintain resting body functions
- Magnetic resonance imaging of the liver and other organs, and of muscle and fat
- Estimation of body fat - measurements of height, weight, hip size, and skin folds over the arms and abdomen to estimate body fat content
- Insulin tolerance test - measures blood glucose levels after administration of insulin. Insulin is given through an intravenous (IV) catheter (a thin tube placed in a vein) and blood is drawn 5 minutes before the test begins, when the test begins, and 5, 10, 15, 20 and 30 minutes into the test
- Oral glucose tolerance test - measures blood glucose and insulin levels after drinking a glucose (sugar) solution. Blood samples are drawn through an IV catheter 15 minutes before the test begins, at the time the test begins, and 30, 60, 90 and 180 minutes into the test
- Intravenous glucose tolerance test - measures tissue response to insulin and glucose after glucose is injected into a vein. The glucose injection is followed by a short infusion of insulin and then blood samples are taken over 3 hours to measure insulin and glucose levels
- Appetite level and food intake - measures hunger level and caloric intake. Patients are questioned about their hunger level, given a variety of foods they may choose to eat and questioned again at various intervals about hunger level. On another day, patients are given breakfast (usually a milkshake) and when they want to eat again, the appetite level and caloric intake study is repeated.
- Hormone function tests - the function of three hormones influenced by leptin (corticotropin-releasing hormone, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone) are assessed. The hormones are injected intravenously and then blood samples are drawn.
When all the tests are completed, leptin therapy begins. The drug is injected under the skin twice a day for 4 months by the patient or a caregiver (similar to self-administered insulin injections for diabetes). Blood is drawn once a month to monitor the effects of treatment and drug side effects. At clinic visits scheduled 1, 2 and 4 months after therapy starts, patients have a physical examination and meet with a dietitian. Medication dosage is also increased at these visits. At the end of 4 months, all baseline studies described above are repeated. Throughout the study, all patients complete a form once a week, in which they record their symptoms. Patients with diabetes also measure their blood glucose levels at home before each meal and at bedtime.
Detailed description
Lipoatrophic diabetes is a syndrome characterized by insulin resistance in association with a paucity of adipose tissue. Patients with severe lipoatrophy die prematurely, typically from the complications of diabetes or liver disease. Experiments with lipoatrophic mice suggest that the insulin resistance is caused by the lack of adipose tissue. Adipose tissue normally produces leptin, a hormone that increases insulin action. To what extent does leptin deficiency cause diabetes in lipoatrophic patients? In one mouse model of lipoatrophy, leptin administration reversed the diabetes and liver disease. In a different, more severely adipose-deficient mouse, the effects of leptin treatment were detectable, but more modest.
In this protocol, to be carried out at both the NIH and the University of Texas in Dallas, we test the hypotheses that leptin can be safely administered to patients with lipoatrophic diabetes and they will benefit from treatment with A-100 (recombinant form of human leptin provided by Amgen). We will study patients with lipoatrophy, low leptin levels, and at least one of the following metabolic abnormalities: severe insulin resistance, diabetes, and/or hypertriglyceridemia.
We will treat patients with A-100 injections for four months, with inpatient studies at baseline, 1, 2, and 4 months of treatment. In the core protocol, we will monitor metabolic control (e.g. glucose, insulin, free fatty acid, and triglyceride levels). Ancillary studies will evaluate the effect of A-100 on the gonadal axis and on liver pathology.
After 8 months of treatment, we will offer a withdrawal study to the patient requiring an inpatient admission and controlled diet. Afterwards leptin therapy will resume in a long-term extension study with follow up visits every 6 months. Metabolic parameters will continue to be followed, along with body fat imaging studies, gonadotropin monitoring, and liver function analysis.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- All ethnic groups
- Males and females
- Age greater than 14 years
- Clinically-significant lipodystrophy, identified by the study physician during the physical examination as an absence of fat outside the range of normal variation and/or identified as a disfiguring factor by the patient.
- Circulating leptin levels less than 4.0 ng/ml in females and less than 3.0 ng/ml in males as measured by Linco assay on at least 2 occasions.
Key exclusion criteria (9 listed)
- General: Pregnant women, women in their reproductive years who do not use an effective method of birth control, women currently nursing or lactating within 6 weeks of having completed nursing, and persons who are unable to provide informed consent will be excluded from the study.
- Exclusions for underlying disease likely to increase side effects or to hinder objective data collection:
- Known liver disease due to causes other than non-alcoholic steatohepatitis
- Current alcohol or substance abuse
- Psychiatric disorder impeding competence or compliance
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 |
|---|---|---|
| hu Leptin (A-100) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9389757Burant CF, Sreenan S, Hirano K, Tai TA, Lohmiller J, Lukens J, Davidson NO, Ross S, Graves RA. Troglitazone action is independent of adipose tissue. J Clin Invest. 1997 Dec 1;100(11):2900-8. doi: 10.1172/JCI119839.
- Background: PubMed 9784492Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, Feigenbaum L, Lee E, Aoyama T, Eckhaus M, Reitman ML, Vinson C. Life without white fat: a transgenic mouse. Genes Dev. 1998 Oct 15;12(20):3168-81. doi: 10.1101/gad.12.20.3168.
- Background: PubMed 10212846Taylor SI, Arioglu E. Syndromes associated with insulin resistance and acanthosis nigricans. J Basic Clin Physiol Pharmacol. 1998;9(2-4):419-39. doi: 10.1515/jbcpp.1998.9.2-4.419. No abstract available.
- Derived from this study: PubMed 37595266Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ. Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491.
- 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 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 hu Leptin (A-100) 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 9 inclusion and 9 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 Mar 2008. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005905, which also lists 6 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 Mar 2008.