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

Primary Purpose

Muscle Cramp, Liver Cirrhosis

Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Pregabalin
Placebo
Sponsored by
Seoul National University Boramae Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscle Cramp focused on measuring muscle cramp, liver cirrhosis, pregabalin

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Seoul Metropolitan Government Boramae Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Pregabalin

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Difference in the frequency of muscle cramps between run-in and treatment phases (/week)
The frequency is defined as muscle cramps per week.

Secondary Outcome Measures

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

Full Information

First Posted
January 6, 2011
Last Updated
March 19, 2020
Sponsor
Seoul National University Boramae Hospital
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01271660
Brief Title
A Study Evaluating the Efficacy and Safety of Pregabalin Against Frequent Muscle Cramp in Patients With Liver Cirrhosis
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 Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
July 2011 (Actual)
Primary Completion Date
February 2018 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Boramae Hospital
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).
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 difference in the frequency of muscle cramps between the run-in and treatment phases. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Cramp, Liver Cirrhosis
Keywords
muscle cramp, liver cirrhosis, pregabalin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pregabalin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pregabalin
Other Intervention Name(s)
Brand name of drug : Lyrica
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Difference in the frequency of muscle cramps between run-in and treatment phases (/week)
Description
The frequency is defined as muscle cramps per week.
Time Frame
after 4 weeks of standard dose treatment period
Secondary Outcome Measure Information:
Title
Response rates , Mean change in the average cramp pain intensity , peripheral nerve excitability , the quality of life, quality of sleep , safety
Description
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.
Time Frame
after 4 weeks of standard dose treatment period or over a 6-week treatment period

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Won Kim, Ph.D.
Organizational Affiliation
SMG-SNU Boramae Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul Metropolitan Government Boramae Medical Center
City
Seoul
ZIP/Postal Code
156-707
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35191232
Citation
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.
Results Reference
derived

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

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