Effects of Metreleptin in Type 1 Diabetes Mellitus
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Leptin
Intervention description: weight based sub-cutaneous injection twice daily of Leptin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes Mellitus

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.
    

Eligibility criteria:

        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 [βhCG]) 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)