Effects of Metreleptin in Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

Official title:

Open Label Single Center Pilot Study to Study Teh Effects of Metreleptin Administration in Patients With Type 1 Diabetes Mellitus ( T1DM ).

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01268644
• Other study ID #: FBA937
• Secondary ID: CTRC # 953
• Status: Terminated
• Phase: Phase 1
• Start date: September 2010
• Est. completion date: August 2014

Study information

• Verified date: July 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will add leptin therapy to the current insulin therapy of Type 1 Diabetics with the aim of lowering the total insulin requirements and suppressing the steep fluctuations typically associated with Type 1 Diabetes.

Description:

The adipocyte hormone, leptin, has been shown to restore the health and glucoregulation of near-death, insulin deficient diabetic rodents. This makes leptin the only hormone, since the discovery of insulin in 1922, with this capability. Leptin normalizes the hyperglucagonemia of diabetes and reduces lipogenesis and cholesterologenenesis. Treatment of diabetic rodents with a combination of leptin and insulin, leads to a stable pattern of glucose control with reduced insulin requirements, as opposed to the high glucose variability that characterizes the treatment of type 1 diabetes with supraphysiologic doses of insulin alone. As such, we will initiate a pilot clinical trial to test combination leptin and insulin therapy in type 1 diabetes. Fifteen leptin sensitive patients (body mass index <27 kg/m²) with uncontrolled diabetes (HbA1c 7.0 to 10.0 %) will be treated with slightly supraphysiologic doses of recombinant human leptin (Amylin Pharmaceuticals). Subjects will be compared to themselves before and after treatment with leptin. Endpoint variables include HbA1c, change in daily insulin dose, mean and standard deviation of blood glucose from inpatient glucose monitoring and glucose meter download. We will also assess effects of leptin therapy on energy intake as assessed by 3-day food record and body weight and fat by DEXA. Intramyocellular and intrahepatic lipid concentration by 1H-MRS will be assessed before and after 3 months of metreleptin therapy. A satiety analysis will be employed. In addition, plasma hormones and inflammatory biomarkers will be assayed during the course of this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: August 2014
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

All of the following criteria are to be fulfilled for inclusion of an individual in the study. An eligible individual:

1. Is male or female and is 18 to 50 years of age

2. Has been diagnosed with T1DM for at least 1 year. Diagnosis of T1DM will be based on clinical criteria including: insulin-dependence within 6 months of the onset, history of prior episode of ketoacidosis, previous documentation of positive serum islet cell autoantibodies or low or undetectable serum C-peptide levels.

3. Has an HbA1c 7.0 to 10.0 %, inclusive

4. Currently on insulin pump or on a combination of basal (long-acting insulin preparation) and pre-prandial (short-acting insulin preparation) insulin therapy

5. Is male, or if female of childbearing potential, is non-lactating, and has a negative pregnancy test (human chorionic gonadotropin, beta subunit [ßhCG]) result at screening (Visit 1) and Visit 2 regardless of menopausal status (If female and of childbearing potential [including peri menopausal women who have had a menstrual period within one year], must practice and be willing to continue to practice appropriate birth control [defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner] during the entire duration of the study.)

6. Has a BMI < 27 kg/m2

7. Has clinical laboratory test values (clinical chemistry, hematology, and urinalysis) judged to be not clinically significant by the investigator at screening (Visit 1)

8. Has a physical examination and electrocardiogram (ECG) with no clinically significant abnormalities as judged by the investigator

Exclusion Criteria:

1. Has a fasting serum triglyceride concentration >400 mg/dL at screening

2. Has hypoglycemia unawareness (Loss of consciousness due to hypoglycemia without preceding symptoms or recent history of blood glucose <50 mg/dl without symptoms)

3. Currently abuses drugs or alcohol, or has a history of abuse that in the investigator's opinion could cause the individual to be noncompliant with study procedures, or has a positive urine screen for drugs of abuse at screening (Visit 1)

4. Has chronic renal insufficiency with serum creatinine > 2 mg/dL

5. Has a history of weight loss (>3%) in the last 3 months

6. Is currently enrolled or plans to enroll in a diet, weight loss, or exercise program

7. Has a sitting blood pressure >160/95 mmHg (either systolic or diastolic) at screening (Visit 1)

8. Has a clinically significant history or presence of any of the following conditions:

• Active cardio- or cerebrovascular disease

• Active pulmonary disease

• Hepatic disease defined as follows:

• At screening (Visit 1), alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase > three times the upper limit of normal (elevated Liver Function Test values suggestive of obesity related non-alcoholic fatty liver disease may not be exclusionary)

• The presence of any other co morbid disorders that, in the opinion of the investigator, would interfere with the subject's compliance of study procedures

• Clinically significant malignancies within 5 years of screening (Visit 1)

• Chronic infections (e.g., HIV [human immunodeficiency virus] or tuberculosis)

9. Has received any investigational drug within 30 days or within a period corresponding to five half-lives of that drug, whichever is greater, before screening (Visit 1)

10. Has had major surgery or a blood transfusion within 2 months before screening (Visit 1) or has a hematocrit < 30%

11. Has a known hypersensitivity to any of the components of the study treatment (e.g. has a known hypersensitivity to E. Coli derived proteins

12. Is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site

13. Is employed by Amylin Pharmaceuticals, Inc., (i.e., an employee, temporary contract worker, or designee responsible for the conduct of the study)

14. Has previously received treatment with recombinant leptin (metreleptin or Fc leptin)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Leptin
weight based sub-cutaneous injection twice daily of Leptin

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Amylin Pharmaceuticals, LLC., Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

References & Publications (1)

Vasandani C, Clark GO, Adams-Huet B, Quittner C, Garg A. Efficacy and Safety of Metreleptin Therapy in Patients With Type 1 Diabetes: A Pilot Study. Diabetes Care. 2017 May;40(5):694-697. doi: 10.2337/dc16-1553. Epub 2017 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c	Change in Hba1c after 12 weeks on Leptin Therapy compared to Baseline value	Baseline and 12 weeks
Secondary	Weight	Change in Body Weight after 12 weeks on Leptin Therapy compared to Baseline value	Baseline to 12 weeks
Secondary	Insulin Dose	Change in Insulin dose after 12 weeks on Leptin Therapy compared to Baseline value	Baseline to 12 weeks
Secondary	Change in HbA1c From Baseline to Week 20 on Leptin Therapy	Change in Hba1c after 20 weeks on Leptin Therapy compared to Baseline value. With ongoing metreleptin therapy, the concomitant basal insulin dose was actively reduced by 50% after week 12.	Baseline to Week 20 (On leptin)