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

This study has been completed.
Sponsor:
Collaborator:
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01006889
First received: November 2, 2009
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

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 (i.e., effects on insulin secretion and insulin action); 3) its impact on weight (i.e., 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 (i.e., hsCRP, ICAM, VCAM, etc.).


Condition Intervention Phase
Nonalcoholic Fatty Liver Disease
Type 2 Diabetes Mellitus
Drug: Exenatide
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A New Treatment Strategy of Adding Exenatide to Insulin Therapy for Patients With Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD)

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Hepatic steatosis as assessed non-invasively by MRS. [ Time Frame: 6 months. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine if in T2DM patients well-controlled on bedtime long-acting detemir and premeal rapid-acting insulin aspart, replacing aspart for exenatide is effective to maintain optimal glycemic control. [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
  • Anthropometric variables (weight, BMI, total body fat by DXA, visceral fat by MRI). [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
  • Patient satisfaction and patient-reported quality of life outcomes. [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
  • Rates of hypoglycemia. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Insulin secretion (hyperglycemic clamp; mixed meal) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Insulin sensitivity (hyperglycemic clamp [M/I]; indexes derived from the mixed meal). [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Plasma inflammatory biomarkers (hsCRP, ICAM, VCAM, etc.) [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
  • Plasma biomarkers of NAFLD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Lipid profiles, lipoprotein analysis by NMR (LipoScience). [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: January 2008
Study Completion Date: February 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide (twice daily)
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
Patients with T2DM well-controlled on an intensified insulin regimen for the previous 6 months by the combination of bedtime insulin detemir (Levemir) and premeal insulin aspart (Novolog) three times daily, 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.
Other Name: Byetta

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  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To enter the study subjects must meet the following criteria:

  1. Have been on intensified insulin therapy with insulin detemir (Levemir) and premeal insulin aspart (Novolog®) for the previous 6 months.
  2. Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent.
  3. 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.
  4. Age range of 18 to 70 years (inclusive).
  5. Patients must have been on a stable dose of allowed chronic medications for 6 months prior to entering the double-blind treatment period.
  6. 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

Exclusion Criteria:

Patients will be excluded if any of the following criteria are present:

  1. Individuals with type 1 diabetes or type 2 diabetes and a FPG ≥ 300 mg/dl; poor compliance with insulin therapy.
  2. Subjects on sulfonylureas, metformin and/or TZDs unless the dose has been stable for at least 6 months prior to study entry.
  3. 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.
  4. Past (within 1 year) or current history of alcohol abuse.
  5. 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006889

Locations
United States, Texas
The University of Texas H.S.C. at San Antonio and the San Antonio Audie L. Murphy VA Hospital
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Amylin Pharmaceuticals, LLC.
Investigators
Principal Investigator: Kenneth Cusi, M.D. The University of Texas H.S.C. at San Antonio and the San Antonio Audie L. Murphy VA Hospital
  More Information

No publications provided

Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01006889     History of Changes
Other Study ID Numbers: HSC20060167-2
Study First Received: November 2, 2009
Last Updated: April 26, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Fatty Liver
Liver Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Exenatide
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 22, 2014