A Randomized Double-Blind Study Testing the Effects of Pregabalin on Diabetic Neuropathy

Study Overview
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Brief Summary
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This study is designed to examine how pregabalin affects parameters of autonomic nerve regulation in correlation with change in pain, anxiety, and depressive symptoms in patients with diabetic neuropathy.

Detailed Description
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This study is designed to primarily examine how pregabalin affects the autonomic nerve or sympathetic-parasympathetic regulation in patients with diabetic neuropathy and its relationship to neuropathic pain. The goals of this study include (1) assessing the change of parameters of autonomic nerve function such as heart rate variability (HRV), respiratory sinus arrhythmia (RSA), minute ventilation, and changes in objective sleep parameters measured by means of the LifeShirt, upon treatment of pregabalin in comparison to placebo; (2) assessing the symptom change of neuropathic pain upon treatment of pregabalin in comparison to placebo; (3) assessing the change of anxiety symptoms upon treatment of pregabalin in comparison to placebo; (4) assessing the change of depressive symptoms upon treatment of pregabalin in comparison to placebo; (5) assessing the relationship of autonomic nerve function with neuropathic pain at baseline prior to treatment and the correspondences to the study drug; (6) assessing the relationship of autonomic nerve function with anxiety and depressive symptoms at baseline prior to treatment and their correspondences to the study drug; (7) identifying sensitive and reliable parameters of autonomic nerve regulation as predictor(s) of the severity and improvement of neuropathic pain and/or anxiety; and (8) to assess the change in objective sleep parameters (EEG/EOG) by means of the LifeShirt, upon treatment of pregabalin in comparison to placebo

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single Center Study Designed to Assess the Effects of Pregabalin on Change in Patients With Diabetic Neuropathy

Conditions
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Diabetic Neuropathy

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients aged 18 years or older Meet criteria for diagnosis of diabetic neuropathy Average daily pain scores greater than or equal to 4 by Visual Analog Scale Ability to give informed consent No pregnancy Exclusion Criteria: Patients with clinically significant psychiatric disorders requiring vigorous interventions, i.e., moderate to severe depressive disorder, psychotic disorders, PTSD, obsessive compulsive disorder, panic disorder, substance abuse, or personality disorders, or active suicidal/homicidal ideations, or past history of active suicidal ideation and/or attempts Patients on gabapentin which cannot be discontinued, meaning a dose greater than 1200mg. If a patient is on a dose of gabapentin that is less than 1200mg and he or she is willing to stop taking the medication, he or she can participate in the study. These patients must take the last dose of gabapentin the night before starting the study. Patients being non-compliant with diabetic control Inability to wear the LifeShirt Unable to participate or answer questions using a personal digital assistant input device

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin<br>Pregabalin medication | Drug: Pregabalin<br>* Subjects will take pregabalin for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.<br>* Other names: Lyrica;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Subjects will take placebo for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing the Change in Resting Blood Pressure Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. |  | baseline and at end of a 4-week intervention | 
| Assessing the Change in Heart Rate by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. | The LifeShirt System, developed by VivoMetrics, is a lightweight vest with embedded sensors that continuously collect information on a range of cardiopulmonary parameters. It was used to collect and store the respiratory rate, posture, activity level, QRS complexes, and R-R intervals via a 3-axis accelerometer and a 3-lead, single channel electrocardiogram. | baseline and at end of a 4-week intervention | 
| Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. | Heart rate variability parameters generated by the frequency domain analysis included: total power (area under the curve) over all frequencies, very low frequency (VLF, 0-0.04 Hz),low frequency (LF, 0.04-0.15 Hz), and high frequency (HF,0.15-0.4 Hz). | baseline and at end of a 4-week intervention | 
| Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. | Heart Rate Variability parameters generated by the frequency domain analysis included: Low Frequency / High Frequency (LF/HF), as well as normalized LF (normalized LF=LF/[total power-VLF]) and normalized HF (normalized HF=HF/[total power-VLF]). | baseline and at end of a 4-week intervention | 
| Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. | Heart rate variability parameters yielded by time domain analysis included the mean of all R-R intervals (ANN), standard deviation of all R-R intervals (SDNN), root mean square of successive differences (RMSSD), and standard deviation of the averages of R-R intervals for all 5-minute segments within the block (SDANN). | baseline and at end of a 4-week intervention | 
| Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. | Heart rate variability parameters yielded by time domain analysis included the number of N-N intervals that differ by more than 50 milliseconds from adjacent intervals divided by the total number of all N-N intervals (pNN50). | baseline and at end of a 4-week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. | Pain severity was evaluated using the Visual Analog Scale, the Modified Brief Pain Inventory-Short Form, and the Neuropathy Pain Scale. The Visual Analog Scale was scored within a range of 0-100 with 0=no pain and 100=the worst imaginable pain. The Brief Pain Inventory is made up of two parts: total pain and pain interference. The total pain score is the sum of most, least, average, and now pain scored within a range of 0-10 with 0=no pain and 10=pain as bad as you can imagine. The pain interference score is the sum of affective and activity interference - how pain interfered with general activity, mood, walking ability, normal work, relationships, sleep, and enjoyment of life. It was scored within a range of 0-10 with 0=pain does not interfere and 10=pain completely interferes. The Neuropathy Pain Scale total is the sum of 10 items -cold, sharp, deep, dull, hot, intense, itchy, sensitive, surface, and unpleasant pain scored within a range of 0-10 with 0=no pain and 10=most pain. | baseline and end of 4 week intervention | 
| To Assess the Change of Anxiety Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. | Anxiety symptoms were measured using the Spielberger State-Trait Anxiety Inventory Scale (STAI) for symptoms of anxiety. State anxiety: score range, 20-80 (higher score=greater levels of state anxiety). Trait anxiety: score range, 20-80 (higher score=greater levels of trait anxiety). | baseline and at end of a 4-week intervention | 
| To Assess the Change of Depressive Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. | The Beck Depression Inventory Scale measures symptoms of depression, score range, 0-63 (higher score=greater severity of depressive symptoms) | baseline and at end of a 4-week intervention | 
| To Assess the Change in Disability Scale Upon Treatment of Pregabalin in Comparison to Placebo. | The Sheehan Disability Scale was used to evaluate functional impairment in work/school, social and family life, score range, 0-10; the 3 items can be summed into a single dimensional measure of global functional impairment that ranges from 0(unimpaired) to 30 (highly impaired). | baseline and at end of a 4-week intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic neuropathy, Pregabalin, Lyrica