The Effects of Short-Term Exenatide Therapy in Newly Diagnosed Type 2 Diabetic Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Taipei Veterans General Hospital, Taiwan
Sponsor:
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier:
NCT01270191
First received: January 3, 2011
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

Whether GLP-1 and GLP-1 receptor agonists will produce a sustained improvement in beta-cell function following short-term therapy is currently not known. This randomized, controlled trial is carried to assess the efficacy of short-term insulin therapy (NPH injection twice daily) compared with GLP-1 analogue (Exenatide injection twice daily) on glycemic control, remission rate, ß-cell function, and long-term glycemic control in newly diagnosed type 2 diabetic patients with moderate hyperglycemia.


Condition Intervention Phase
Type 2 Diabetes
Drug: Exenatide
Drug: Humulin-N
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Short-Term Exenatide Therapy on the Beta-Cell Function and Long-term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Taipei Veterans General Hospital, Taiwan:

Primary Outcome Measures:
  • the time of glycemic remission and remission rate [ Time Frame: at one year ] [ Designated as safety issue: No ]
    The primary outcomes are the time of glycemic remission and remission rate at one year after short-term therapy.

  • The time of monotherapy failure and monotherapy failure rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The primary outcomes at 5 years are long-term glycemic control. After 5 months of intensive therapy, these patients were off medication and follow up in our clinics. When diabetes relapsed, they will be treated with metformin monotherapy. The monotherapy failure is defined as A1C >7.0% with metformin 1500 mg per day.


Secondary Outcome Measures:
  • Beta-cell function and insulin sensitivity calculated from OGTT. [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    The Beta-cell function and insulin sensitivity calculated from OGTT.

  • Comparison of A1C change, the proportion of subjects who reached the treatment target [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
    The secondary outcomes are the comparison of A1C change, the proportion of subjects who reached the treatment target (A1C <7.0% or <6.5%) at 6 months and 12 months.

  • Comparison of A1C change, the proportion of subjects who reached the treatment target [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    These subjects will be followed up for 5 years to evaluate their long-term glycemic control. The secondary outcomes are the comparison of A1C change, the proportion of subjects who reached the treatment target (A1C <7.0% or <6.5%) at 5 years.


Estimated Enrollment: 160
Study Start Date: November 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide
In the exenatide therapy group, subjects will be instructed in the techniques for injection and be treated with 5 mcg bid for 4 weeks and then 10 mcg bid for 12 weeks. They also visit every 2 weeks in the first 2 visits and then every month until 4 months. If FPG still greater than 200 mg/dL after 4 weeks of exenatide treatment, they will use insulin for rescue therapy and will be withdrawn from this study.
Drug: Exenatide
They will be treated with 5 mcg bid for 4 weeks and then 10 mcg bid for 12 weeks. They also visit every 2 weeks in the first 2 visits and then every month until 4 months.
Other Name: Byetta
Active Comparator: Humulin-N
In the insulin therapy group (Humulin-N), subjects will be instructed in the techniques for insulin injection and home capillary glucose monitoring. The insulin dose will be initiated with 0.25 unit/Kg per day, and the two thirds of daily dose will be administrated before breakfast and the other will be administrated at bedtime. Insulin doses will be titrated every 3 days to achieve target fasting blood glucose values between 70 and 130 mg/dl.
Drug: Humulin-N
The insulin dose will be initiated with 0.25 unit/Kg per day, and the two thirds of daily dose will be administrated before breakfast and the other will be administrated at bedtime. Insulin doses will be titrated every 3 days to achieve target fasting blood glucose values between 70 and 130 mg/dl.
Other Name: NPH insulin

Detailed Description:

Background: There is a progressive deterioration in beta-cell function in type 2 diabetics, and it was estimated that islet function was about 50% of normal at the time of diagnosis. The progressive nature of type 2 diabetes is one of the major challenges in the treatment of affected patients, and agents that could alter the natural history of this condition would add greatly to current treatment approaches. Short-term intensive insulin therapy of newly diagnosed type 2 diabetes will improve beta-cell function and usually leading to a temporary remission time. The acute effect of GLP-1 and GLP-1 receptor agonists on beta-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis and stimulation of insulin gene transcription. The chronic action is stimulating beta-cell proliferation, induction of islet neogenesis, and inhibition of ß-cell apoptosis, thus promoting expansion of beta-cell mass, as observed in rodent diabetes and in cultured beta-cells.

Objectives: Whether GLP-1 and GLP-1 receptor agonists will produce a sustained improvement in beta-cell function following short-term therapy is currently not known. This randomized, controlled trial is carried to assess the efficacy of short-term insulin therapy (NPH injection twice daily) compared with GLP-1 analogue (Exenatide injection twice daily) on glycemic control, remission rate, beta-cell function, and long-term glycemic control in newly diagnosed type 2 diabetic patients with moderate hyperglycemia.

Study Designs and Methods: We will recruit 80 newly diagnosed type 2 diabetic patients with moderate hyperglycemia, and another 80 newly diagnosed type 2 diabetic patients with severe hyperglycemia who receive intensive insulin therapy for 10-14 days, and will be randomized to be treated with exenatide or insulin injections. They will visit our clinics every 2 weeks in the first 2 visits and then every 4 weeks for 20 weeks. After the 24 weeks of intervention, all patients will be treated with life style modification only and follow fasting plasma glucose every month. Hyperglycemia relapse is defined as fasting plasma glucose more than 126 mg/dL and confirmed two weeks later. Patients with hyperglycemia relapse will be treated with metformin (from 500 mg per day to 1500 mg per day)and then gliclazide-MR will be added to as the second step for the remaining study period. A1C measurement will be performed at baseline, 3, 6, 12 and 18 months, and OGTT will be performed at screen and after 6 months of randomization. All of these subjects were continually followed-up in our clinics for 5 years to evaluate their long-term glycemic control. The monotherapy failure is defined as A1C >7.0% with metformin 1500 mg/day.

The primary outcomes at one year are the time of glycemic remission and remission rate at one year after short-term therapy. The primary outcomes at 5 years are monotherapy failure time and monotherapy failure rate at 5 years after short-term therapy. The secondary outcomes are the beta-cell function and insulin sensitivity calculated from OGTT, the comparison of A1C change, the proportion of subjects who reached the treatment target (A1C <7.0% or <6.5% at 1 and 5 years). These subjects will be followed up for 5 years to evaluate their long-term glycemic control.

Expected Results: We will expect to screen 100 patients, randomize 80 patients and there will be at least 30 patients in each group complete the one year follow-up. We expected that short-term intensive treated with both insulin and exenatide can get better glycemic control accompanied with improving the beta-cell function in newly diagnosed type 2 diabetes. We can compare the remission rate at one year after different short-term therapy. We will further evaluate the effects on the beta-cell function and long-term glycemic control. This study also can assess what readily available parameter would predict which patients will achieve long-term successful glycemic control after correction of glucose toxicity.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Newly diagnosed type 2 diabetic patients.
  2. Age between 30 and 70 years old.
  3. HbA1C between 7 and 9% in OPD patients
  4. If HbA1c >9.0% of blood glucose >300 mg/dL, intensive insulin therapy for 10-14 days

Exclusion Criteria:

  1. Previous treated with anti-diabetic medication
  2. Pregnant or lactation women.
  3. Impaired liver function (ALT > 100 U/L)
  4. Impaired renal function (Serum creatinine >2.0 mg/dL)
  5. Recently suffered from MI or CVA.
  6. Patients are acute intercurrent illness.
  7. 2-hour C-peptide level < 2.0 ng/mL.
  8. History of severe hypersensitivity to any product components.
  9. History or high risk of acute pancreatitis.
  10. Now use warfarin.
  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: NCT01270191

Locations
Taiwan
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan, 11217
Contact: Harn-Shen Chen, MD, PhD    886-2-28757515    chenhs@vghtpe.gov.tw   
Principal Investigator: Harn-Shen Chen, MD, PhD         
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
Investigators
Principal Investigator: Harn-Shen Chen, MD, PhD Taipei Veterans General Hospital, Taiwan
  More Information

No publications provided

Responsible Party: vghtpe user, Taipei Veterans General Hospital, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier: NCT01270191     History of Changes
Other Study ID Numbers: VGHIRB 201010013MB
Study First Received: January 3, 2011
Last Updated: June 26, 2013
Health Authority: Taiwan: Department of Health

Keywords provided by Taipei Veterans General Hospital, Taiwan:
Exenatide, Beta-Cell Function, Glycemic Control
in Newly Diagnosed Type 2 Diabetic Patients

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

ClinicalTrials.gov processed this record on September 18, 2014