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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Seoul National University Boramae Hospital
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Won Kim, Seoul National University Boramae Hospital
ClinicalTrials.gov Identifier:
NCT01271660
First received: January 6, 2011
Last updated: July 31, 2014
Last verified: July 2014
  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

Resource links provided by NLM:


Further study details as provided by Seoul National University Boramae Hospital:

Primary Outcome Measures:
  • 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)]


Secondary Outcome Measures:
  • 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 2015
Estimated Primary Completion Date: December 2014 (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
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 < 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271660

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

Locations
Korea, Republic of
Seoul Metropolitan Government Boramae Medical Center Recruiting
Seoul, Korea, Republic of, 156-707
Contact: Young Jung Moon, RN, CRC    82-2-870-2857    god3718@hanmail.net   
Principal Investigator: Won Kim, Ph.D.         
Sponsors and Collaborators
Seoul National University Boramae Hospital
Pfizer
Investigators
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: July 31, 2014
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
Muscle Cramp
Digestive System Diseases
Liver Diseases
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Signs and Symptoms
Gamma-Aminobutyric Acid
Pregabalin
Analgesics
Anticonvulsants
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
GABA Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014