Trial Outcomes & Findings for Evaluation of Exenatide in Patients With Diabetic Neuropathy (NCT NCT00855439)

Last Updated: 2017-03-01

Results Overview

CCN was defined by a composite score comprised of at least two positive responses among symptoms, sensory signs, or absent or hypoactive reflexes consistent with a distal symmetrical polyneuropathy (16), and at least one abnormal nerve conduction study result in two anatomically distinct nerves, e.g. the sural sensory and peroneal motor nerves (defined as a amplitude \< 5 μV and a conduction velocity \< 40 m/sec for the sural nerve and an amplitude \< 2.5 μV and a conduction velocity \< 40 m/sec for the peroneal nerve).

Recruitment status

COMPLETED

Study phase

Target enrollment

46 participants

Primary outcome timeframe

18 Months

Results posted on

2017-03-01

Participant Flow

Date of first patient randomized to treatment:10/29/2008 Date of last patient randomized to treatment:12/07/2012

After obtaining written informed consent, participants were asked to provide medical history. A physical examination was performed, with specific focus on signs and symptoms of peripheral neuropathy. Baseline labs were obtained. Eligible subjects were invited for a baseline visit at which detailed neurologic assessment were done.

Participant milestones

Participant milestones
Measure	Exenatide Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Overall Study STARTED	22	24
Overall Study COMPLETED	19	24
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Exenatide Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Overall Study Withdrawal by Subject	2	0
Overall Study Pregnancy	1	0

Baseline Characteristics

Evaluation of Exenatide in Patients With Diabetic Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exenatide n=22 Participants Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=24 Participants Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control	Total n=46 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=93 Participants	20 Participants n=4 Participants	36 Participants n=27 Participants
Age, Categorical >=65 years	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants
Age, Continuous	51 years STANDARD_DEVIATION 13 • n=93 Participants	54 years STANDARD_DEVIATION 9 • n=4 Participants	53 years STANDARD_DEVIATION 10 • n=27 Participants
Gender Female	9 Participants n=93 Participants	11 Participants n=4 Participants	20 Participants n=27 Participants
Gender Male	13 Participants n=93 Participants	13 Participants n=4 Participants	26 Participants n=27 Participants
Region of Enrollment United States	22 participants n=93 Participants	24 participants n=4 Participants	46 participants n=27 Participants

PRIMARY outcome

Timeframe: 18 Months

Outcome measures

Outcome measures
Measure	Exenatide n=22 Participants Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=24 Participants Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Confirmed Clinical Neuropathy (CCN)	14 participants	18 participants

SECONDARY outcome

Timeframe: 18 months

Group differences in E/I ratio, a measure of cardiac autonomic function.

Outcome measures

Outcome measures
Measure	Exenatide n=19 Participants Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=24 Participants Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Cardiac Autonomic Neuropathy (CAN)	1.1 unit-less measure Standard Deviation 0.1	1.1 unit-less measure Standard Deviation 0.4

SECONDARY outcome

Timeframe: 18 month

resting heart rate as marker of autonomic function at rest

Outcome measures

Outcome measures
Measure	Exenatide n=19 Participants Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=24 Participants Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Cardiac Autonomic Neuropathy	70 beats per minute Standard Deviation 9	77 beats per minute Standard Deviation 10

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Subset of study population

Exploratory endpoint: Regeneration of intra-epidermal nerve fibers after denervation by capsiacin.

Outcome measures

Outcome measures
Measure	Exenatide n=11 Participants Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=11 Participants Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Intra-epidermal Nerve Fiber Density	2.1 nerve fibers per mm of skin Standard Deviation 3.5	4.6 nerve fibers per mm of skin Standard Deviation 2.9

Adverse Events

Exenatide

Serious events: 6 serious events

Other events: 9 other events

Deaths: 0 deaths

Glargine

Serious events: 8 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Exenatide n=22 participants at risk Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=24 participants at risk Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
General disorders Non-Serious Adverse Event	40.9% 9/22 • Number of events 17 • From Screening to Study End: 1 year 7 months	79.2% 19/24 • Number of events 39 • From Screening to Study End: 1 year 7 months

Additional Information

Rodica Pop-Busui, MD, PhD

University of Michigan

Phone: 734 647-9809

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Exenatide n=22 participants at risk Subjects will take exenatide by subcutaneous injection twice daily for 18 months Exenatide: Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels	Glargine n=24 participants at risk Subjects will take 1 daily injection of insulin glargine for 18 months. Glargine: Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control
Cardiac disorders Atrial Fibrillation	0.00% 0/22 • From Screening to Study End: 1 year 7 months	8.3% 2/24 • Number of events 2 • From Screening to Study End: 1 year 7 months
Cardiac disorders Coronary Artery Bypass Graft	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Cardiac disorders Congestive Heart Failure	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 2 • From Screening to Study End: 1 year 7 months
Respiratory, thoracic and mediastinal disorders Status Asthmaticus	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Neuroendocrine Tumor	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Reproductive system and breast disorders Pregnancy	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Gastrointestinal disorders Diverticulitis	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Gastrointestinal disorders Cholilithiasis	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Endocrine disorders Thyroidectomy	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	0.00% 0/24 • From Screening to Study End: 1 year 7 months
Cardiac disorders Non-ST elevation myocardial infarction	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Gastrointestinal disorders Incarcerated Ventral Hernia	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Skin and subcutaneous tissue disorders foot ulcer with cellulitis	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Musculoskeletal and connective tissue disorders Amputation of Toe	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Musculoskeletal and connective tissue disorders Bone Fracture	4.5% 1/22 • Number of events 1 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months
Endocrine disorders Severe Hypoglycemia	0.00% 0/22 • From Screening to Study End: 1 year 7 months	4.2% 1/24 • Number of events 1 • From Screening to Study End: 1 year 7 months