Diabetic Peripheral Neuropathy, Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Neuropathy, Glucose, Control, Peripheral, Autonomic
Brief summary
This study will look at whether or not the medication exenatide improves signs and symptoms of diabetic peripheral neuropathy in people with type 2 diabetes and mild to moderate diabetic peripheral neuropathy.
Detailed description
This study will look at the effects of the medication exenatide on peripheral neuropathy in people with type 2 diabetes. Exenatide (trade name, BYETTA®) is an injectable medication used by people with type 2 diabetes to control blood sugar. Peripheral neuropathy is a complication of diabetes that can cause symptoms such as numbness, tingling or burning sensations in the feet and hands. Controlling blood sugars levels in type 2 diabetes is thought to prevent, delay or improve the damage to the nerve fibers that causes peripheral neuropathy. There is also some evidence that exenatide may have additional beneficial effects on the peripheral nerves, beyond the benefits of blood sugar control alone. In this study, about half of the participants will take exenatide by injection twice daily and the other half will take insulin glargine (Lantus®) by injection once daily. Both groups are expected to have similar improvement in blood sugar control. This study will show whether exenatide has beneficial effects on neuropathy beyond the benefits of better blood sugar control alone.
Interventions
DRUGExenatide
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
DRUGGlargine
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
Sponsors
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes treated with one or more oral agents * Persistent fasting glucose \> 140 mg/dl or HbA1c \> 7% * Stable and maximally effective doses of one or more oral agents for 3 months * Presence of diabetic peripheral neuropathy * Age between 18 and 70 years * No risk factors or other causes of neuropathy * Willingness and capacity to sign the Institutional Review Board approved consent form and cooperate with the medical procedures for study duration
Exclusion criteria
* Nursing mothers or pregnant women * A history of previous kidney, pancreas or cardiac transplantation * A past history of neuropathy (independent of diabetes) or with a disease known to be associated with neuropathy (e.g., hepatitis C, end stage renal disease, lupus) * Amputation of any part of either lower extremity for any reason or traumatic loss of any part of either lower extremity or congenital absence or severe deformity of lower extremity * HbA1c \> 10% * Participation in an experimental medication trial within 3 months of starting the study. * Undergoing therapy for malignant disease other than basal- or squamous cell carcinoma * Requiring long-term glucocorticoid therapy * Inability or unwillingness to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Clinical Neuropathy (CCN) | 18 Months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Autonomic Neuropathy (CAN) | 18 months | Group differences in E/I ratio, a measure of cardiac autonomic function. |
| Cardiac Autonomic Neuropathy | 18 month | resting heart rate as marker of autonomic function at rest |
Other
| Measure | Time frame | Description |
|---|---|---|
| Intra-epidermal Nerve Fiber Density | 12 months | Exploratory endpoint: Regeneration of intra-epidermal nerve fibers after denervation by capsiacin. |
Countries
United States
Participant flow
Recruitment details
Date of first patient randomized to treatment:10/29/2008 Date of last patient randomized to treatment:12/07/2012
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 22 |
| 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 | 24 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Glargine | Exenatide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 16 Participants | 36 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 9 | 51 years STANDARD_DEVIATION 13 | 53 years STANDARD_DEVIATION 10 |
| Gender Female | 11 Participants | 9 Participants | 20 Participants |
| Gender Male | 13 Participants | 13 Participants | 26 Participants |
| Region of Enrollment United States | 24 participants | 22 participants | 46 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 22 | 19 / 24 |
| serious Total, serious adverse events | 6 / 22 | 8 / 24 |
Outcome results
Primary
Confirmed Clinical Neuropathy (CCN)
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).
Time frame: 18 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Confirmed Clinical Neuropathy (CCN) | 14 participants |
| Glargine | Confirmed Clinical Neuropathy (CCN) | 18 participants |
Secondary
Cardiac Autonomic Neuropathy
resting heart rate as marker of autonomic function at rest
Time frame: 18 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Cardiac Autonomic Neuropathy | 70 beats per minute | Standard Deviation 9 |
| Glargine | Cardiac Autonomic Neuropathy | 77 beats per minute | Standard Deviation 10 |
Secondary
Cardiac Autonomic Neuropathy (CAN)
Group differences in E/I ratio, a measure of cardiac autonomic function.
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Cardiac Autonomic Neuropathy (CAN) | 1.1 unit-less measure | Standard Deviation 0.1 |
| Glargine | Cardiac Autonomic Neuropathy (CAN) | 1.1 unit-less measure | Standard Deviation 0.4 |
Other Pre-specified
Intra-epidermal Nerve Fiber Density
Exploratory endpoint: Regeneration of intra-epidermal nerve fibers after denervation by capsiacin.
Time frame: 12 months
Population: Subset of study population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Intra-epidermal Nerve Fiber Density | 2.1 nerve fibers per mm of skin | Standard Deviation 3.5 |
| Glargine | Intra-epidermal Nerve Fiber Density | 4.6 nerve fibers per mm of skin | Standard Deviation 2.9 |