A 17-Week Trial To Assess Pregabalin For The Treatment Of Nerve Pain Due To Spinal Cord Injury

Phase 3

Completed

Conditions: Neuralgia
Spinal Cord Injuries

Interventions: Drug: placebo
Drug: pregabalin

Registration Number: NCT00407745

Lead Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Brief Summary: The purpose of this study is to evaluate if pregabalin relieves nerve pain associated with spinal cord injury compared to placebo (pill that contains no active medicine). This study will also evaluate the safety of pregabalin in this patient population.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 220

Inclusion Criteria

Subjects with nerve pain after Spinal cord injury (traumatic, diving, ischemic and after removal of benign tumors (except meningioma and fibromas)
Pain has to be chronic(continuous for at least 3 months or intermittent for at least 6 months
Pain score at least 4 in 4 of 7 days prior to receive treatment.

Exclusion Criteria

Pregabalin use in the last 60 days, prior intolerance to pregabalin
Creatinine clearance <60 mL/min.
White blood cell count <2500/mm3; neutrophil count <1500/mm3; platelet count <100 x 103/ mm3.
Abuse of drugs or alcohol
Unstable medial conditions
Clinically significant abnormal electrocardiogram (ECG).
Presence of severe pain associated with conditions other than spinal cord injury that could confound the assessment or self-evaluation of pain due to spinal cord injury.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
matched placebo	placebo	-
pregabalin	pregabalin	flexible dosing over 4 weeks followed by 12 weeks maintenance and one week taper period

Primary Outcome Measures

Name	Time	Method
Duration Adjusted Average Change (DAAC) of Mean Pain Score	Baseline, Week 16	DAAC was derived from participant's daily pain diary, where pain was measured on an 11-point Numerical Rating Scale (NRS-Pain)ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). The DAAC was calculated as the mean of all daily pain diary rating post baseline minus the baseline score then multiplied by the proportion of the planned study duration completed by the participant.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Weekly Mean Pain Score	Baseline, Week 16	Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).
Number of Participants With >=30% Reduction in Weekly Mean Pain Score From Baseline	Baseline, Week 16	Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale)	Baseline, Week 16	The PGIC is a participant-rated instrument measuring change in the participant's overall status on a 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.
Change From Baseline in Weekly Mean Sleep Interference Score	Baseline, Week 16	Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]).
Change From Baseline in Weekly Mean Pain Score by Week	Baseline, Week 1 through16	Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).
Number of Participants With >=50% Reduction in Weekly Mean Pain Score From Baseline	Baseline, Week 16	Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).
Change From Baseline in Modified Brief Pain Inventory Interference Scale (10-Item) (mBPI-10) Total Score	Baseline, Week 16	The Modified Brief Pain Inventory (mBPI-10) Interference Scale is a self administered questionnaire that assessed pain interference with functional activities over the past week. The items were measured on an 11 point scale, ranging from "does not interfere" (0) to "completely interferes" (10). A composite score, the pain interference index, was calculated by averaging the 10 items that comprised the scale.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Static Mechanical Allodynia	Baseline, Week 16	Participant rated pain scale. The pain produced by the applied stimulus (static mechanical allodynia - gentle constant mechanical pressure) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Dynamic Mechanical Allodynia	Baseline, Week 16	Participant rated pain scale. The pain produced by the applied stimulus (dynamic mechanical allodynia - gentle stroking with foam brush) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Punctata Hyperalgesia	Baseline, Week 16	Participant rated pain scale. The pain produced by the applied stimulus (Punctata hyperalgesia - pinprick) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Temporal Summation to Tactile Stimuli	Baseline, Week 16	Participant rated pain scale. The pain produced by the applied stimulus (Temporal summation to tactile stimuli - repeated touching/tapping) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Allodynia	Baseline, Week 16	Participant rated pain scale. The pain produced by the applied stimulus (Cold allodynia - touch with cool metal rod 13-17 degrees celsius was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Hyperalgesia Subscales	Baseline, Week 16	Participant rated pain scale. The pain produced by the applied stimulus (Cold hyperalgesia - touch with cold metal rod 4 degrees celsius) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - 12 Items Total Intensity Score	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Burning Spontaneous Pain	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Pressing Spontaneous Pain	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paroxysmal Pain	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Evoked Pain	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paresthesia/Dysesthesia	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score	Baseline, Week 16	Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.
Number of Participants With Improved Duration of Brief Pain Attacks Based on NPSI - Duration (Item 4)	Baseline, Week 16	NPSI - Temporal item which assesses the duration (number of hours during the last 24 hours) of spontaneous ongoing pain. Improved duration would be a decrease in the number of hours of spontaneous ongoing pain during the last 24 hours compared to baseline.
Number of Participants With Improvement in the Number of Attacks Based on NPSI - Number of Attacks (Item 7)	Baseline, Week 16	NPSI - Temporal item which assesses the paroxysmal pain (number of pain attacks during the last 24 hours). Improvement in the number of attacks would be a decrease in the number of paroxysms during the last 24 hours compared to baseline.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS)- 9-Item Overall Sleep Problems Index	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Adequacy	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Snoring	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Awaken Short of Breath or With a Headache	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Quantity	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Somnolence	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Number of Participants Having Optimal Sleep Based on Medical Outcomes Study Sleep Scale (MOS-SS)	Baseline, Week 16	Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Anxiety	Baseline, Week 16	HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.
Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Depression	Baseline, Week 16	HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.