Role of Exenatide in Type 1 Diabetes

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00456300
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 11
• Location: 1
• Arms: 3
• Actual Duration (Months): 24
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to see if giving exenatide and insulin before a meal would lower blood sugars after the meal. This study may help in developing new treatments to help control high blood sugars after meals. This may help improve overall blood sugar control and prevent the long-term effects of diabetes.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Exenatide; Drug: Insulin	Phase 2

Detailed Description

A large study in people with type 1 diabetes (T1DM) showed that lowering blood sugars stopped or delayed the occurrence of health problems. As a result of the study, treatment should try to control blood sugars as near to normal as safely possible.

In people without diabetes, the "after meal" blood sugar level is very carefully controlled. Insulin (the hormone that lowers blood sugar) and glucagon (hormone that raises blood sugar) play a key role in keeping this careful balance. It is now known that a substance made by the body called GLP-1 also helps with this careful balance. Glucagon like peptide-1 works in four ways. First, it helps to stimulate the cells in the pancreas to produce more insulin. Secondly, it helps to "dampen" the glucagon response (glucagon is released after a meal and causes the blood sugar to rise). Thirdly, Glucagon like peptide-1 delays the digestion of food in the stomach. Lastly, it seems to "dampen" the appetite, which causes a person to eat less.

Exenatide is a medication that works very similar to Glucagon like peptide-1. Exenatide is FDA approved for use in adults.

Study Design: Followed by a baseline study with insulin alone, subjects were randomized to two different doses of exenatide (1.25 and 2.5 µ,g), administered in a double-blinded randomized controlled manner, along with insulin as a single subcutaneous injection. Studies were at least 3 weeks apart.

Baseline: At 0800 h, the pre-breakfast insulin bolus was administered based on patient's usual insulin-to-carbohydrate ratio. Post-bolus, subjects drank 12 ounces of a standard liquid meal (Boost High Protein Drink, 360 calories, 50 g carbohydrates, and 12 g fat), enriched with 1 g of [13C] glucose within 10 min. Breath samples for 13CO2 analysis were collected in duplicates at 17 time points until 1300 h. Usual insulin basal rates or glargine were maintained during study.

On the days subjects received the study drug of 1.25 µ,g (~0.02 µ,g/kg) or 2.5 µ,g (~0.04 µ,g/kg) exenatide along with insulin, the prandial insulin was reduced by 20%.

Measurements: Plasma glucose was measured using a bedside YSI glucose analyzer (2300 Stat Plus; Yellow Springs Instruments, Yellow Springs, OH) throughout the study at regularly timed intervals. Delta plasma glucose area under the curve (AUC0 -120) was measured for the exenatide treated groups vs. insulin monotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Role of Exenatide in Type 1 Diabetes Mellitus
• Actual Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide 1.25 mcg + Insulin In each intervention arm the participant receives a different dose of Exenatide along with Insulin as a single subcutaneous injection	Drug: Exenatide; In each intervention arm the participant receives a different dose (1.25 or 2.5 mcg) of exenatide.; Other Names: Byetta ; Drug: Insulin; Each subject received a baseline study with insulin alone
Experimental: Exenatide 2.5 mcg + Insulin In each intervention arm the participant receives a different dose of Exenatide along with Insulin as a single subcutaneous injection	Drug: Exenatide; In each intervention arm the participant receives a different dose (1.25 or 2.5 mcg) of exenatide.; Other Names: Byetta ; Drug: Insulin; Each subject received a baseline study with insulin alone
Active Comparator: Insulin Each subject received a baseline study with insulin alone	Drug: Insulin; Each subject received a baseline study with insulin alone

Outcome Measures

Primary Outcome Measures

1. Mean Plasma Glucose Area Under the Curve (AUC) for Blood Glucose Concentration in the Exenatide 1.25 mcg or Exenatide 2.5 mcg Treated Groups Along With Insulin, Compared to Insulin Alone [0-120 minutes post-dose]

   Post-prandial blood glucose concentration in terms of mean AUC (0-120 min) was determined in subjects treated with either Exenatide 1.25 mcg or Exenatide 2.5 along with insulin, compared to insulin alone, given as a single subcutaneous injection

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects must be patients of the Texas Children's Hospital Diabetes Care Center .

All of the following criteria must be met:

1. Between 12-21 years of age at the time of enrollment.

2. Have been diagnosed with Type 1 diabetes for at least 1 year and in good control (HbA1C less than 8.5%).

3. Subjects must be otherwise healthy except for the Type 1 Diabetes and treated hypothyroidism.

4. Menstruating women must have a negative pregnancy test.

5. Hemoglobin equal to or greater than 12 g/dL before each study.

6. Weight greater than 44 kg.

7. Tanner stage greater than 3

Exclusion Criteria:

1. Any chronic disease: leukemia, asthma, inflammatory bowel disease, cystic fibrosis, juvenile rheumatoid arthritis etc or on treatment that might directly or indirectly affect glucose homeostasis, except for diabetes and hypothyroidism; stable on medications.

2. Lack of a supportive family environment as detected by the clinicians and/or social workers.

3. Positive pregnancy test in menstruating young women.

4. BMI greater than 90th percentile for age or less than 10th percentile for age.

5. Lactating and nursing mothers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Texas Children's Hospital/ Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Montefiore Medical Center
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Rubina Heptulla, MD, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rubina Heptulla, Principal Investigator, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT00456300
• Other Study ID Numbers: H-16488
• First Posted: Apr 4, 2007
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Rubina Heptulla, Principal Investigator, Montefiore Medical Center: Hypoglycemia; Hyperglycemia
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Exenatide

Study Results

Participant Flow

Recruitment Details	11 subjects were enrolled into the study. Of these, 9 subjects were randomized and only 8 subjects completed this three part study. These subjects were recruited from the diabetes clinics.
Pre-assignment Detail	Two subjects failed screening and could not be randomized to particiapate.

Arm/Group Title	Insulin First, Then Exenatide1.25 mcg, Then Exenatide 2.5 mcg	Insulin First, Then Exenatide 2.5 mcg, Then Exenatide 1.25 mcg
Arm/Group Description	Each of the eight study subjects underwent three study visits at-least 3 weeks apart; at each visit receiving either Insulin alone, Exenatide 1.25 mcg + Insulin or Exenatide 2.5 mcg + Insulin	Each of the eight study subjects underwent three study visits at-least 3 weeks apart; at each visit receiving either Insulin alone, Exenatide 2.5 mcg + Insulin or Exenatide 1.25 mcg + Insulin
Period Title: Overall Study
STARTED	5	4
COMPLETED	4	4
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Following the baseline study with insulin, Participants were randomized to receive either Exenatide 1.25 mcg or Exenatide 2.5 mcg
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	17 (1)
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Mean Plasma Glucose Area Under the Curve (AUC) for Blood Glucose Concentration in the Exenatide 1.25 mcg or Exenatide 2.5 mcg Treated Groups Along With Insulin, Compared to Insulin Alone
Description	Post-prandial blood glucose concentration in terms of mean AUC (0-120 min) was determined in subjects treated with either Exenatide 1.25 mcg or Exenatide 2.5 along with insulin, compared to insulin alone, given as a single subcutaneous injection
Time Frame	0-120 minutes post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of each intervention and completed all study visits were included in the analyses. Only 8 subjects completed all study visits and one dropped out during the second study visit.

Arm/Group Title	Exenatide 1.25 mcg + Insulin	Exenatide 2.5 mcg + Insulin	Insulin Monotherapy
Arm/Group Description	Participants who received Exenatide 1.25 mcg along with Insulin as a single subcutaneous injection	Participants who received Exenatide 2.5 mcg along with Insulin as a single subcutaneous injection	Participants who received Insulin alone as a single subcutaneous injection, part of baseline study
Measure Participants	8	8	8
Mean (Standard Error) [mmol*L/min]	49 (156)	44 (281)	379 (259)

Adverse Events

Time Frame	0-120 minutes post-dose
Arm/Group Title	Exenatide 1.25 mcg + Insulin		Exenatide 2.5 mcg + Insulin		Insulin Monotherapy
Arm/Group Description	Participants who received Exenatide 1.25 mcg along with Insulin as a single subcutaneous injection		Participants who received Exenatide 2.5 mcg along with Insulin as a single subcutaneous injection		Participants who received Insulin alone as a single subcutaneous injection, as part of the baseline study visit
All Cause Mortality
	Exenatide 1.25 mcg + Insulin		Exenatide 2.5 mcg + Insulin		Insulin Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/9 (0%)
Serious Adverse Events
	Exenatide 1.25 mcg + Insulin		Exenatide 2.5 mcg + Insulin		Insulin Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide 1.25 mcg + Insulin		Exenatide 2.5 mcg + Insulin		Insulin Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		0/9 (0%)		0/9 (0%)
Endocrine disorders
Hypoglycemia	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.