Diabetic Peripheral Neuropathy
Conditions
Brief summary
The purpose of this study is to see if an investigational drug known as the lidocaine 5% patch is safe and effective in reducing the symptoms of diabetic neuropathy, to examine how topical lidocaine affects the nerve endings, and to determine whether treatment with the lidocaine patch can prevent the potential progression to chronic diabetic neuropathy pain in subjects who did not report pain at the start of the study.
Interventions
PROCEDURESkin biopsy
Skin biopsy specimens will processed and analyzed for Nerve fiber count, nerve and skin morphology, and sodium channel specific epitope expression in keratinocytes.
DRUGLidocaine 5% patches
Subject will apply patches to affected area QD for 12 hours then remove.
Sponsors
Endo Pharmaceuticals
Albany Medical College
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Group 1: 18-70 years of age, non-diabetic with no nervous system disease (healthy control group) * Group 2: 18-70 years of age with Type I or Type II diabetes with significantly painful diabetic neuropathy (VAS \> 40mm at Baseline) * Group 3: 18-70 years of age with Type I or Type II diabetes with non- painful or insignificantly painful diabetic neuropathy (VAS \< 40mm at Baseline)
Exclusion criteria
* History of clinically significant liver disease, serious peripheral vascular disease, a blood clotting disorder, or any other medical condition felt to be exclusionary by the investigator * Allergy to lidocaine * Unwillingness to sign informed consent or any other reasons for which the investigator feels the subject cannot complete the study * Women who are pregnant, breastfeeding or trying to become pregnant * History of slow-healing diabetic foot ulcers * Current skin or soft tissue lesions on the foot that will interfere with application of the lidocaine patch and or skin biopsies * Subjects taking Class I antiarrhythmics * HgA1c \> 11% * Active cancer within the previous two years except treated basal cell carcinoma of the skin * Co-morbidities that can produce neuropathy * Subjects taking sodium channel blockers within one week of study treatment and throughout the study * Subjects taking any other experimental drugs within 30 days prior to Screening Visit (Visit 1) * Application of lidocaine patch to either foot within two weeks of Screening Visit (Visit 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores From Composite Visual Analog Scale | baseline, 4 weeks | Scores range from 0 to 10 with higher scores indicating higher levels of pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Baseline, 4 weeks | Pixel intensity (0-256) of immunofluorescence for each individual biomarker. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control Patients Subjects 18 to 70 years of age, non-diabetic with no nervous system disease. Lidocaine 5% patch applied to both feet daily, Skin biopsies at biaseline and end of study.
Skin biopsy: Skin biopsy specimens will processed and analyzed for Nerve fiber count, nerve and skin morphology, and sodium channel specific epitope expression in keratinocytes.
Lidocaine 5% patches: Subject will apply patches to affected area QD for 12 hours then remove. | 11 |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy 18 to 70 years old with significantly painful diabetic neuropathy.Lidocaine 5% patch applied to both feet daily, Skin biopsies at biaseline and end of study.
Skin biopsy: Skin biopsy specimens will processed and analyzed for Nerve fiber count, nerve and skin morphology, and sodium channel specific epitope expression in keratinocytes.
Lidocaine 5% patches: Subject will apply patches to affected area QD for 12 hours then remove. | 21 |
| Patients With Non-painful Diabetic Peripheral Neuropathy 18-70 years of age with Type I or Type II diabetes with non-painful or insignificantly painful diabetic neuropathy.Lidocaine 5% patch applied to both feet daily, Skin biopsies at baseline, 4 weeks, and end of study.
Skin biopsy: Skin biopsy specimens will processed and analyzed for Nerve fiber count, nerve and skin morphology, and sodium channel specific epitope expression in keratinocytes.
Lidocaine 5% patches: Subject will apply patches to affected area QD for 12 hours then remove. | 12 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Screen Failure | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | Healthy Control Patients | Type I or Type II Diabetes With Painful Diabetic Neuropathy | Patients With Non-painful Diabetic Peripheral Neuropathy | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 19 Participants | 10 Participants | 40 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 8 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 21 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 21 | 0 / 12 |
Outcome results
Primary
Pain Scores From Composite Visual Analog Scale
Scores range from 0 to 10 with higher scores indicating higher levels of pain.
Time frame: baseline, 4 weeks
Population: Healthy controls were not assessed for this measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Pain Scores From Composite Visual Analog Scale | Baseline | 6.5 units on a scale |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Pain Scores From Composite Visual Analog Scale | 4 weeks | 4.5 units on a scale |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Pain Scores From Composite Visual Analog Scale | Baseline | 1.2 units on a scale |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Pain Scores From Composite Visual Analog Scale | 4 weeks | 0.5 units on a scale |
Secondary
Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP
Pixel intensity (0-256) of immunofluorescence for each individual biomarker.
Time frame: Baseline, 4 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Healthy Control Patients | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.6-baseline | 81.2 Pixel intensity (0-256) |
| Healthy Control Patients | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.6-4 weeks | 91 Pixel intensity (0-256) |
| Healthy Control Patients | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.7-baseline | 47.5 Pixel intensity (0-256) |
| Healthy Control Patients | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.7-4 weeks | 52.4 Pixel intensity (0-256) |
| Healthy Control Patients | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | CGRP-baseline | 27.7 Pixel intensity (0-256) |
| Healthy Control Patients | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | CGRP-4 weeks | 31.5 Pixel intensity (0-256) |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | CGRP-4 weeks | 32.8 Pixel intensity (0-256) |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.6-baseline | 101.4 Pixel intensity (0-256) |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.7-4 weeks | 51.5 Pixel intensity (0-256) |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | CGRP-baseline | 38.5 Pixel intensity (0-256) |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.6-4 weeks | 90.7 Pixel intensity (0-256) |
| Type I or Type II Diabetes With Painful Diabetic Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.7-baseline | 59.6 Pixel intensity (0-256) |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.6-4 weeks | 90.8 Pixel intensity (0-256) |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.7-baseline | 54.3 Pixel intensity (0-256) |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | CGRP-4 weeks | 26.2 Pixel intensity (0-256) |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.7-4 weeks | 54.7 Pixel intensity (0-256) |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | Nav1.6-baseline | 87.9 Pixel intensity (0-256) |
| Patients With Non-painful Diabetic Peripheral Neuropathy | Keratinocyte Immunoreactivity of Nav1.6, Nav1.7, CGRP | CGRP-baseline | 29.5 Pixel intensity (0-256) |