Effects of Metreleptin in Type 1 Diabetes Mellitus

July 17, 2019 updated by: Abhimanyu Garg, University of Texas Southwestern Medical Center

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: active open label Leptin
Active open label Leptin for type 1 Diabetes
Drug: Leptin
weight based sub-cutaneous injection twice daily of Leptin
Other Names:
  • Metreleptin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
HbA1c
Time Frame: Baseline and 12 weeks
Change in Hba1c after 12 weeks on Leptin Therapy compared to Baseline value
Baseline and 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight
Time Frame: Baseline to 12 weeks
Change in Body Weight after 12 weeks on Leptin Therapy compared to Baseline value
Baseline to 12 weeks
Insulin Dose
Time Frame: Baseline to 12 weeks
Change in Insulin dose after 12 weeks on Leptin Therapy compared to Baseline value
Baseline to 12 weeks
Change in HbA1c From Baseline to Week 20 on Leptin Therapy
Time Frame: Baseline to Week 20 (On leptin)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Texas Southwestern Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Juvenile Diabetes Research Foundation
Amylin Pharmaceuticals, LLC.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Abhimanyu Garg, M.D., UT Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 29, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 30, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 31, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FBA937
  • CTRC # 953 (Other Grant/Funding Number: JDRF and Amylin)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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