Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00025883
Status:
COMPLETED
Last Update Posted:
2016-08-16
First Post:
2001-10-27
Brief Title:
Leptin to Treat Lipodystrophy
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Long-Term Efficacy of Leptin Replacement in Treatment of Lipodystrophy
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the safety and effectiveness of leptin replacement therapy in patients with lipodystrophy also called lipoatrophy Patients have a total or partial loss of fat cells They also lack the hormone leptin which 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 large appetite and liver disease due to fat accumulation
Patients age greater than or equal to 6 months with significant lipodystrophy may be eligible for this study Participants will be admitted to the NIH Clinical Center for 10 days for the following studies before beginning 12 months of leptin therapy
Insulin tolerance test
Ultrasound of the liver and if abnormalities are found possibly liver biopsies
Fasting blood tests
Resting metabolic rate
Magnetic resonance imaging of the liver and other organs and of muscle and fat
Pelvic ultrasound in women to detect ovarian cysts
Estimation of body fat
Oral glucose tolerance test
Intravenous glucose tolerance test
Appetite level and food intake
Hormone function tests
Questionnaires to assess activity and mood
24-hour urine collections
Additional studies may include blood tests for genetic studies of lipodystrophy a muscle biopsy to study muscle proteins involved in regulating energy expenditure before and after leptin replacement and examination of a surgical specimen if available to study molecules that may be involved in energy storage and use
When the above tests are completed leptin therapy begins The drug is injected under the skin twice a day for 4 months and then once a day if feasible The dose is increased at the 1- and 2-month visits Follow-up visits at 1 2 4 6 8 and 12 months after therapy starts include a physical examination blood tests and a meeting with a dietitian At the end of 12 months all baseline studies described above are repeated Patients record their symptoms weekly throughout the study Those with diabetes measure their blood glucose levels daily before each meal and at bedtime
Patients age greater than or equal to 6 months with significant lipodystrophy may be eligible for this study Participants will be admitted to the NIH Clinical Center for 10 days for the following studies before beginning 12 months of leptin therapy
Insulin tolerance test
Ultrasound of the liver and if abnormalities are found possibly liver biopsies
Fasting blood tests
Resting metabolic rate
Magnetic resonance imaging of the liver and other organs and of muscle and fat
Pelvic ultrasound in women to detect ovarian cysts
Estimation of body fat
Oral glucose tolerance test
Intravenous glucose tolerance test
Appetite level and food intake
Hormone function tests
Questionnaires to assess activity and mood
24-hour urine collections
Additional studies may include blood tests for genetic studies of lipodystrophy a muscle biopsy to study muscle proteins involved in regulating energy expenditure before and after leptin replacement and examination of a surgical specimen if available to study molecules that may be involved in energy storage and use
When the above tests are completed leptin therapy begins The drug is injected under the skin twice a day for 4 months and then once a day if feasible The dose is increased at the 1- and 2-month visits Follow-up visits at 1 2 4 6 8 and 12 months after therapy starts include a physical examination blood tests and a meeting with a dietitian At the end of 12 months all baseline studies described above are repeated Patients record their symptoms weekly throughout the study Those with diabetes measure their blood glucose levels daily 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 For the last fourteen years we have been studying the extent to which leptin deficiency causes diabetes in lipoatrophic patients In fact in our initial study we have seen nearly 60 amelioration of fasting glucose triglycerides and free fatty acid levels and about 2 actual decreases from baseline HbA1c levels with 4 months of leptin replacement therapy This response has continued to be sustained as we continue to follow patients that have now received leptin replacement therapy for fourteen years
This is an open-labeled study The study monitors the safety and efficacy of recombinant methionyl human leptin A-100 replacement in children and adults We are looking at the long-term effects of leptin replacement on extended therapy In this long-term replacement protocol we will monitor metabolic control eg glucose insulin and triglyceride levels as primary outcome measures Ancillary studies will evaluate the effect of Metreleptin on other hormonal axes growth and development and on liver pathology
We continue to evaluate the efficacy in a broader leptin deficient population of patients with lipodystrophy Current inclusion criteria in patients greater than or equal to 5 years include female patients with leptin levels 12 ngmL and male patients with leptin levels 8 ngmL We continue to seek patients who meet these criteria In children ages 6 months 5 years we will use a cut-off leptin level of 6 ngmL in both genders
Patients who are greater than or equal to age 5 years will be evaluated every 6 months during the first year of therapy If no improvements are seen after 6 months of therapy then the study medication may be increased to 150 of the predicted dose 009mgkgday for males and girls less than 10 years of age 012mgkgday for females 10 years of age and older from 6 months to 1 year on therapy If no improvements are seen after increasing to 150 of the predicted dose then the study medication will be withdrawn If the patient shows improvements in hisher metabolic parameters while on leptin the patient will be invited to continue taking the study medication The investigators will strive for all patients responding to leptin to bring their metabolic parameters into the normal range The maximum dose of leptin that will be given is 024 mgkgday for females 10 and older and 012 mgkgday for males and females less than 10 years of age After the first year of treatment the patient will be evaluated every 6 months through the second year of treatment and then the study period will end After two years of treatment extending the treatment period on an annual basis will be the decision of the patient principal investigator and Bristol-Myers Squibb BMSAstraZeneca Pharmaceuticals AZ Leptin is supplied by BMSAZ and is currently only available through research studies Neither the NIH nor BMSAZ can guarantee that leptin will be available indefinitely andor after the study ends However leptin was recently approved by the FDA on February 25 2014 for use in patients with generalized lipodystrophy
All patient referrals for acceptance into the protocol are initiated by the physicianhealth care provider
This is an open-labeled study The study monitors the safety and efficacy of recombinant methionyl human leptin A-100 replacement in children and adults We are looking at the long-term effects of leptin replacement on extended therapy In this long-term replacement protocol we will monitor metabolic control eg glucose insulin and triglyceride levels as primary outcome measures Ancillary studies will evaluate the effect of Metreleptin on other hormonal axes growth and development and on liver pathology
We continue to evaluate the efficacy in a broader leptin deficient population of patients with lipodystrophy Current inclusion criteria in patients greater than or equal to 5 years include female patients with leptin levels 12 ngmL and male patients with leptin levels 8 ngmL We continue to seek patients who meet these criteria In children ages 6 months 5 years we will use a cut-off leptin level of 6 ngmL in both genders
Patients who are greater than or equal to age 5 years will be evaluated every 6 months during the first year of therapy If no improvements are seen after 6 months of therapy then the study medication may be increased to 150 of the predicted dose 009mgkgday for males and girls less than 10 years of age 012mgkgday for females 10 years of age and older from 6 months to 1 year on therapy If no improvements are seen after increasing to 150 of the predicted dose then the study medication will be withdrawn If the patient shows improvements in hisher metabolic parameters while on leptin the patient will be invited to continue taking the study medication The investigators will strive for all patients responding to leptin to bring their metabolic parameters into the normal range The maximum dose of leptin that will be given is 024 mgkgday for females 10 and older and 012 mgkgday for males and females less than 10 years of age After the first year of treatment the patient will be evaluated every 6 months through the second year of treatment and then the study period will end After two years of treatment extending the treatment period on an annual basis will be the decision of the patient principal investigator and Bristol-Myers Squibb BMSAstraZeneca Pharmaceuticals AZ Leptin is supplied by BMSAZ and is currently only available through research studies Neither the NIH nor BMSAZ can guarantee that leptin will be available indefinitely andor after the study ends However leptin was recently approved by the FDA on February 25 2014 for use in patients with generalized lipodystrophy
All patient referrals for acceptance into the protocol are initiated by the physicianhealth care provider
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-DK-0022 | OTHER | National Institutes of Health Clinical Center | None |