Adding Exenatide to Insulin Therapy for Patients With Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease

NCT01006889 | Completed Phase 4 Results

• 1 other identifier: HSC20060167-2
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of the study is to determine the impact on hepatic steatosis of replacing premeal rapid-acting insulin for exenatide (Byetta) while maintaining bedtime long-acting detemir (Levemir) insulin in well-controlled patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Secondary aims are to learn: 1) the efficacy and safety of such approach and whether it is an acceptable treatment strategy compared to intensified insulin therapy alone; 2) mechanisms of action (effects on insulin secretion and insulin action); 3) its impact on weight (can it prevent insulin-associated weight gain or cause weight loss) and rates of hypoglycemia; 4) if it may improve specific plasma biomarkers of disease activity in NAFLD and inflammatory markers common to both conditions - T2DM and NAFLD (hsCRP, ICAM, VCAM).

Conditions

Nonalcoholic Fatty Liver Disease; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Hepatic Steatosis

  Hepatic steatosis was assessed non-invasively by MRS.

  6 months

Secondary Outcomes (7)

• A1c

  6 months

• Change in Anthropometric Variables (Weight).

  6 months

• Number of Severe Hypoglycemic (Glucose ≤40 mg/dL) Events.

  6 months

• Insulin Secretion (Hyperglycemic Clamp)

  6 months

• Percent Change From Baseline in Glucose Infusion (M Value) During Hyperglycemic Clamp

  6 months

Study Arms (1)

Exenatide (twice daily)

EXPERIMENTAL

Patients with T2DM well-controlled on an intensified insulin regimen for the previous 6 months by the will have their insulin aspart discontinued and replaced for exenatide twice daily while continuing the bedtime detemir insulin. Safety and efficacy parameters will be measured before and after 6 months of treatment.

Drug: Exenatide

Interventions

Exenatide DRUG

The participants with T2DM well-controlled on an intensified insulin regimen for the previous 6 months with the combination of a premeal insulin injection of the drug aspart (Novolog) three times a day and a bedtime insulin injection of the drug detemir (Levemir). The dosage of the insulin is determined by the need by the need of the participant. The Exenatide treatment will consist of an injection of the insulin twice daily and will replace the premeal insulin regiment of aspart.

Also known as: Byetta

Exenatide (twice daily)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To enter the study subjects must meet the following criteria:
• Have been on intensified insulin therapy with insulin detemir (Levemir) and premeal insulin aspart (Novolog®) for the previous 6 months.
• Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent.
• Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period.
• Age range of 18 to 70 years (inclusive).
• Patients must have been on a stable dose of allowed chronic medications for 6 months prior to entering the double-blind treatment period.
• All participants must have the following laboratory values:
• Hemoglobin ≥12 g/dl in males or ≥11 g/dl in females Serum creatinine ≤1.5 mg/dl AST (SGOT) and ALT (SGPT) ≤2.5 times upper limit of normal Alkaline phosphatase ≤2.5 times upper limit of normal

You may not qualify if:

• Patients will be excluded if any of the following criteria are present:
• Individuals with type 1 diabetes or type 2 diabetes and a FPG ≥ 300 mg/dl; poor compliance with insulin therapy.
• Subjects on sulfonylureas, metformin and/or TZDs unless the dose has been stable for at least 6 months prior to study entry.
• Patients on any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on stable doses of such agents for the past two months before entry into the study. Patients may be taking stable doses of estrogens or other hormonal replacement therapy if the patient has been on these agents for the prior two months. Patients taking systemic glucocorticoids will be excluded.
• Past (within 1 year) or current history of alcohol abuse.
• Patients will be excluded if there is a history of clinically significant heart disease (New York Heart Classification greater than grade II), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) or chronic renal failure (serum creatinine greater than 1.5 mg/dl).

Sponsors & Collaborators

• University of Florida: lead
• Amylin Pharmaceuticals, LLC.: collaborator

Study Sites (1)

The University of Texas H.S.C. at San Antonio and the San Antonio Audie L. Murphy VA Hospital

San Antonio, Texas, 78229-3900, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Dr. Kenneth Cusi
• Organization: University of Florida

kcusi@ufl.edu

352-273-8661

Study Officials

• Kenneth Cusi, M.D.

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2009
• First Posted: November 3, 2009
• Study Start: January 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: February 1, 2010
• Last Updated: September 28, 2016
• Results First Posted: July 29, 2016

Record last verified: 2016-06

Locations

US (1)