Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005905
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2000-06-09
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:
Efficacy of Leptin Replacement in Treatment of Lipodystrophy
Status:
COMPLETED
Status Verified Date:
2003-04
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 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
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 andor 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 eg 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
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 andor 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 eg 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 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 |
|---|---|---|---|
| 00-DK-0146 | None | None | None |