A Study Evaluating the Efficacy and Safety of Pregabalin Against Frequent Muscle Cramp in Patients With Liver Cirrhosis
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Purpose
Muscle cramp is defined as a paroxysmal, involuntary, and painful contraction of skeletal muscle. Cirrhotic patients can encounter with muscle cramp frequently, which might be associated with poor quality of life. Gabapentin can be prescribed for muscle cramp. However, patients with liver cirrhosis have limited access to gabapentin which is metabolized primarily in liver.
Pregabalin with a similar mechanism of action to gabapentin undergoes negligible metabolism owing to its improved pharmacokinetic properties. Thus, pregabalin might be a promising therapeutic option for patients with liver cirrhosis who are suffering from muscle cramp and susceptible to drug-induced hepatotoxicity.
Therefore, the investigators hypothesize that pregabalin could effectively reduce painful symptoms derived from muscle cramp. In the current study, the investigators are going to evaluate the efficacy and safety of pregabalin by comparing outcomes between two groups (treatment group vs. placebo group).
| Condition | Intervention | Phase |
|---|---|---|
|
Muscle Cramp Liver Cirrhosis |
Drug: Pregabalin Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver) Primary Purpose: Treatment |
| Official Title: | A Randomized, Double-blinded, Placebo-controlled Study Evaluating the Efficacy and Safety of 6-week Treatment of Pregabalin Against Frequent Muscle Cramp in Patients With Liver Cirrhosis |
- mean reduction rates of the frequency of muscle cramps between pregabalin and placebo groups [ Time Frame: after 4 weeks of standard dose treatment period ] [ Designated as safety issue: No ]Definition of the reduction rate of the frequency of muscle cramps is defined as [(a total number of muscle cramps during the run-in period) - (a total number of muscle cramps during the standard dose treatment period)] divided by [(a total number of muscle cramps during the run-in period)]
- Response rates , Mean change in the average cramp pain intensity , peripheral nerve excitability , the quality of life, quality of sleep , safety [ Time Frame: after 4 weeks of standard dose treatment period or over a 6-week treatment period ] [ Designated as safety issue: Yes ]
Response rates : the proportion (%) of patients showing ≥50% reduction in the number of muscle cramps.
Mean change in the average cramp pain intensity : a sum of the pain rating scale divided by a total number of muscle cramps.
Peripheral nerve excitability as measured by nerve stimulation test.
The quality of life as measured by mean change in the score of the SF-36.
Quality of sleep as measured by mean change in the number of muscle cramps during sleep.
Safety as measured by dose-reduction or discontinuation rates, treatment-emergent adverse events, and vital signs.
| Estimated Enrollment: | 70 |
| Study Start Date: | July 2011 |
| Estimated Study Completion Date: | March 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Pregabalin
35 randomly allocated patients after a 4-week run-in period, who will take part in a 6-week treatment period with pregabalin. Treatment period : 75 mg twice daily during the first 1 week as titration + 150mg twice daily for 4 weeks as standard dose period + 75mg twice a day for a week as tapering period. |
Drug: Pregabalin
drug form : capsule, 75/150mg. Pregabalin will be provided to treatment arm subjects for 6-week Treatment period. Treatment period : 75 mg twice daily during the first 1 week as titration + 150mg twice daily for 4 weeks as maintenance + 75mg twice a day as tapering Other Name: Brand name of drug : Lyrica
|
|
Placebo Comparator: Placebo
35 randomly allocated patients after a 4-week run-in period, who will take part in a 6-week treatment period with placebo. Treatment period : 75 mg twice daily during the first 1 week as titration + 150mg twice daily for 4 weeks as standard dose period + 75mg twice a day for a week as tapering period. |
Drug: Placebo
drug form : capsule, 75/150mg. Pregabalin will be provided to treatment arm subjects for 6-week Treatment period. Treatment period : 75 mg twice daily during the first 1 week as titration + 150mg twice daily for 4 weeks as maintenance + 75mg twice a day as tapering Other Name: Placebo
|
Detailed Description:
The investigators are planning to recruit patients with liver cirrhosis and muscle cramp, and collect the baseline clinical and laboratory data during the 4-week run-in period for each subject. After a run-in period, there will be the second step of patient selection to achieve a more homogenous study population. Then, patients will be randomly allocated into the treatment (pregabalin) and placebo (dummy) arms, by a web-based randomization program. After a treatment period (75 mg twice daily during the first 1 week as titration, 150 mg twice daily for 4 weeks as standard dose), the investigators will gather further study information of a standard dose period (150mg twice daily for 4 weeks) from the target population and the study subjects will enter the 1-week tapering period (75mg twice a day) to discontinuation. The primary outcome will be the reduction rate of the frequency of muscle cramps between pregabalin and placebo treatment groups. The investigators also intend to assess the response rate, defined as the proportion (%) of patients showing ≥50% reduction in the number of muscle cramps, mean change in the average pain intensity, mean change in the score of the Short Form 36 (SF-36, QualityMetric) health survey questionnaire, mean change in the frequency of muscle cramps during sleep, and mean change in the average cramp threshold frequency by the neurophysiologic study (nerve excitability test) and analyze the reasons for drop-out cases.
Eligibility| Ages Eligible for Study: | up to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria: (should follow all conditions described below)
- Etiology : Liver cirrhosis patients of any etiology, whether viral or non-viral
- Occurrence of muscle cramp equal to or more than 2 times a week over the last month
Exclusion Criteria:
- Preexisting disease : Occlusive vascular disease, thyroid disease, peripheral neuropathy
- Drugs within 2 months : Digitalis, cimetidine, clofibrate, lithium, opiate, nifedipine, beta-agonist, beta-blocker, penicillamine, gabapentin, pregabalin, tricyclic anti-depressant, carbamazepine, phenytoin, quinidine, antispastic drugs, verapamil, vitamin E, branched chain amino acid, excessive alcohol consumption (male >40 g/day, female >20 g/day)
- Underlying disease : Renal impairment (Ccr < 60mL/min), neuromuscular disease (stroke, cerebral palsy, multiple sclerosis, Parkinson disease, progressive muscular dystrophy, epilepsy), suicidal attack, drug allergy, pregnancy, heart failure
- Liver status : Serious complications resulting from decompensated cirrhosis except ascites, such as portosystemic encephalopathy, acute variceal bleeding within the past 3 months from study entry
- CNS or PNS or muscular disease, stroke, cerebral palsy, multiple sclerosis, Parkinson disease, progressive muscular dystrophy, epilepsy
- The previous episode of suicidal attack
- Drug hypersensitivity
- Subjects receiving antiepileptic drugs
- Patients manipulating machines or driving cars
- Pregnant women
- Subjects with congestive heart failure requiring medications
- Galactose-Lactose metabolic abnormality
- Refractory ascites to medical treatment
Contacts and Locations| Contact: Won Kim, Ph.D. | 82-2-870-2233 | drwon1@snu.ac.kr |
| Korea, Republic of | |
| Seoul Metropolitan Government Boramae Medical Center | Recruiting |
| Seoul, Korea, Republic of, 156-707 | |
| Contact: Jin-Ho Cho 82-2-870-2851 acondition@naver.com | |
| Principal Investigator: Won Kim, Ph.D. | |
| Principal Investigator: | Won Kim, Ph.D. | Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center |
More Information
No publications provided
| Responsible Party: | Won Kim, MD, PhD, Assistant Professor, Seoul National University Boramae Hospital |
| ClinicalTrials.gov Identifier: | NCT01271660 History of Changes |
| Other Study ID Numbers: | 06-2010-132, IG-KOR-014-2010 |
| Study First Received: | January 6, 2011 |
| Last Updated: | April 21, 2013 |
| Health Authority: | Korea: Food and Drug Administration |
Keywords provided by Seoul National University Boramae Hospital:
|
muscle cramp liver cirrhosis pregabalin |
Additional relevant MeSH terms:
|
Liver Cirrhosis Fibrosis Muscle Cramp Liver Diseases Digestive System Diseases Pathologic Processes Muscular Diseases Musculoskeletal Diseases Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases |
Signs and Symptoms Pregabalin Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Anticonvulsants |
ClinicalTrials.gov processed this record on May 23, 2013