The Effect of Pregabalin on Pain Related to Walking in Patients With Diabetic Peripheral Neuropathy

A Randomized, Double-blind, Placebo-Controlled, Cross-over Study on the Effect of Pregabalin on Pain Related to Walking in Patients With Diabetic Peripheral Neuropathy

The hypothesis of this study is that pregabalin, 150 mg bid, will reduce general daytime pain in patients diagnosed with diabetic peripheral neuropathy and that it will also reduce the level of pain associated with walking. Consequently, it is hypothesized that the reduction in pain will result in an increase in the amount of walking they do during the day, improvements in their gait, balance, risk of falls and sleep patterns.

Study Overview

• Status: Completed
• Conditions: Diabetic Peripheral Neuropathy; Nerve Pain
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebo

Detailed Description

Pregabalin (LYRICA®) is a potent and specific ligand at the alpha-2-delta subunit of voltage-gated calcium channels. It is currently approved for adjunctive therapy for neuropathic pain conditions. Patients with diabetic peripheral neuropathy suffer from pain in their feet which interferes with their ability to walk which includes less walking, an altered gait, and altered balance. At night the peripheral neuropathy also interferes with their sleep patterns.The hypothesis of this study is that pregabalin, 150 mg bid, will reduce general daytime pain in patients diagnosed with diabetic peripheral neuropathy and that it will also reduce the level of pain associated with walking. Consequently, it is hypothesized that the reduction in pain will result in an increase in the amount of walking they do during the day, improvements in their gait, balance, risk of falls and sleep patterns.Pain and sleep quality will be assessed with questionnaires but objective measurements will be used to assess gait, balance, daytime activities (including walking) and sleep patterns.

Statistical Power Calculations were based on the fact that this is a randomized, double-blind, placebo-controlled, 2-period crossover study to be conducted at a single site. Comparisons will be drawn at baseline, at the completion of each 6 weeks of treatment/placebo arm. The study has been powered at 0.80 for a two-tail analysis with a sensitivity to detect a 30% delta in pain perception in 40 subjects. From previous studies, the cross-over design suggested has achieved significance with 20 patients per group. Forty-four patients will be recruited in total. Significance will be established at an alpha level of 0.05. Both parametric and non parametric correlations will be carried out between the different variables measured and progressive logistic regression to determine the relative contributions of pain relief on the primary and secondary variables being measured in the study.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23510f
      • Eastern Virgnia Medical School, Strelitz Diabetes Center
    • Norfolk, Virginia, United States, 23510
      • Strelitz Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals with painful, peripheral neuropathy (ages 40-75 years) and type 2 diabetes (n=40).

Exclusion Criteria:

• Active ocular or systemic disease
• Recent or recurrent history of musculoskeletal injury,
• Presence of neurological conditions or idiopathic neuropathy
• History of or vertigo
• Use of an aid while walking or difficulty with standing upright
• Visible tremor or uncorrected visual deficits.
• Presence of type 1 diabetes mellitus (defined as C-peptide < 1 ng/ml or diabetes onset at < 35 years of age in a non-obese patient).
• Presence of diabetic retinopathy that is more severe than "background" level.
• Presence of diabetic nephropathy
• Presence of clinically significant neuropathy that is clearly of non-diabetic origin, e.g. alcoholic or autoimmune.
• Bilateral amputation of lower extremities or foot ulcers involving the great toes.
• Presence of neuroarthropathy (Charcot deformity) is allowable.
• History of major macrovascular events such as myocardial infarction or stroke within the past 6 months.
• Patients with moderate or severe hepatic insufficiency or abnormalities of liver function.
• Presence of significant pedal edema.
• Other serious medical conditions that in the opinion of the investigator, would compromise the subject's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: pregabalin at 150 mg bid; Each subject was randomized to the treatment for 6 weeks, followed by a 2 week washout period, and then completed the other arm of the study.	Drug: Pregabalin; 150mg bid; Other Names: Lyrica
PLACEBO_COMPARATOR: Placebo; Each subject was randomized to the treatment for 6 weeks, followed by a 2 week washout period, and then completed the other arm of the study.	Drug: Placebo; 150mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in fall risk associated with walking assessed with the Physiological Profile Assesment	The falls risk will also be ascertained using the long-form Physiological Profile Assessment. The Physiological Profile Assessment has been validated in prospective studies of falls in both community and institutional settings, and predicts those at increased risk of falling with 75-79% accuracy. The Physiological Profile Assessment includes tests of vision (edge contrast sensitivity, high/low contrast visual acuity, depth perception), sensation (ankle touch sensitivity, leg proprioception), leg muscle strength (knee flexion, knee extensors, ankle dorsiflexion), postural sway and postural coordination. Scores from each of these physiologic tests are combined to provide an overall fall risk score that ranges from -2 (very low risk) to +4 (very marked risk).	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-assessed change in pain intensity assessed with an 11-point scale	Based on an 11-point scale assessed after walking 50 ft in a laboratory setting.	Up to 6 months
Sleep quality assessed with the Medical Outcomes Study Sleep Scale questionnaire	assessed at home with the Medical Outcomes Study Sleep Scale questionnaire to be completed in the morning.	Up to 6 months
Patient Global Impression of Change (PGIC)	Patients will record pain and sleep information in diaries. The Patient Global Impression of Change is a 7-point scale on which patients will rate any change in their overall status that they had experienced since beginning study medication from much improved to much worse. The Patient Global Impression of Change is also a 7-point scale on which the clinician rated the change observed in the patient's overall status since the beginning of the study.	Up to 6 months

Collaborators and Investigators

• Sponsor: Eastern Virginia Medical School
• Collaborators: Old Dominion University
• Investigators: Principal Investigator: Aaron I Vinik, PhD, MD, Eastern Virginia Medical School

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (ESTIMATE): October 7, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 7, 2016
• Last Update Submitted That Met QC Criteria: October 6, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Peripheral Neuropathy; Diabetic Pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Neuralgia; Peripheral Nervous System Diseases; Diabetic Neuropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 10-11-FB-0209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO