A Study Evaluating the Efficacy and Safety of Pregabalin Against Frequent Muscle Cramp in Patients With Liver Cirrhosis

Condition(s) targeted: Muscle Cramp; Liver Cirrhosis

Intervention: Pregabalin (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Seoul National University Boramae Hospital

Official(s) and/or principal investigator(s):
Won Kim, Ph.D., Principal Investigator, Affiliation: Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center

Overall contact:
Won Kim, Ph.D., Phone: 82-2-870-2233, Email: drwon1@snu.ac.kr

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).

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Primary outcome: mean reduction rates of the frequency of muscle cramps between pregabalin and placebo groups

Secondary outcome: Response rates , Mean change in the average cramp pain intensity , peripheral nerve excitability , the quality of life, quality of sleep , safety

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.

Minimum age: N/A. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

Won Kim, Ph.D., Phone: 82-2-870-2233, Email: drwon1@snu.ac.kr

Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Korea, Republic of; Recruiting
Jin-Ho Cho, Phone: 82-2-870-2851, Email: acondition@naver.com
Won Kim, Ph.D., Principal Investigator

Starting date: July 2011
Last updated: July 6, 2012