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

NCT01271660 | Completed Phase 3

• 2 other identifiers: 06-2010-132IG-KOR-014-2010
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Muscle Cramp; Liver Cirrhosis

Keywords

muscle cramp; liver cirrhosis; pregabalin

Outcome Measures

Primary Outcomes (1)

• Difference in the frequency of muscle cramps between run-in and treatment phases (/week)

  The frequency is defined as muscle cramps per week.

  after 4 weeks of standard dose treatment period

Secondary Outcomes (1)

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

  after 4 weeks of standard dose treatment period or over a 6-week treatment period

Study Arms (2)

Pregabalin

ACTIVE COMPARATOR

30 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

Placebo

PLACEBO COMPARATOR

30 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

Interventions

Pregabalin DRUG

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

Also known as: Brand name of drug : Lyrica

Pregabalin

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \< 60 mL/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
• central nervous system (CNS) or peripheral nervous system (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

Sponsors & Collaborators

• Seoul National University Boramae Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Seoul Metropolitan Government Boramae Medical Center

Seoul, 156-707, South Korea

Location

Related Publications (1)

• Ahn S, Hong YH, Lee DH, Joo SK, Jung YJ, Sohn SY, Choi K, Kim W. Efficacy and Safety of Pregabalin for Muscle Cramps in Liver Cirrhosis: A Double-Blind Randomized Controlled Trial. J Korean Med Sci. 2022 Feb 21;37(7):e56. doi: 10.3346/jkms.2022.37.e56.

  PMID: 35191232 DERIVED

MeSH Terms

Conditions

Muscle Cramp; Liver Cirrhosis

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Won Kim, Ph.D.

  SMG-SNU Boramae Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Assistant Professor

Study Record Dates

• First Submitted: January 6, 2011
• First Posted: January 7, 2011
• Study Start: July 1, 2011
• Primary Completion: February 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 20, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)