Safety and Efficacy of Baclofen for Treatment of Muscle Spasms in Patients With Cirrhosis: A Pilot Study

• Sponsor: University of Virginia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02298868
• Collaborator: (none)
• Enrollment: 10
• Arm: 1
• Duration (Months): 25

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of the medication Baclofen for treatment of muscle cramps in patients with cirrhosis.

Condition or Disease	Intervention/Treatment	Phase
Muscle Cramps; Cirrhosis	Drug: Baclofen	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Baclofen for Treatment of Muscle Spasms in Patients With Cirrhosis: A Pilot Study
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.	Drug: Baclofen

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Headache) [4 weeks of active therapy]

   Proportion of patients with headache at any time during the 4 weeks of therapy

2. Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Nausea) [4 weeks of active therapy]

   Proportion of patients with nausea at any time during the 4 weeks of therapy

3. Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Dizziness) [4 weeks of active therapy]

   Proportion of patients with dizziness at any time during the 4 weeks of therapy

4. Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Encephalopathy) [4 weeks of active therapy]

   Proportion of patients with endephalopathy at any time during the 4 weeks of therapy

5. Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Somnolence) [4 weeks of active therapy]

   Proportion of patients with somnolence at any time during the 4 weeks of therapy

Secondary Outcome Measures

1. Efficacy of Baclofen to Change Frequency of Muscle Cramps in Patients With Cirrhosis at the End of 4 Weeks of Therapy [Baseline to 4 weeks of therapy]

   Patients undertook a muscle cramp questionnaire prior to treatment that measured frequency in the number of days in a week that a subject experienced muscle cramps. This measures was repeated after 4 weeks of therapy and reported as the mean decrease in frequency of muscle cramps (4 weeks of therapy-Baseline).

2. Efficacy of Baclofen to Change Severity of Muscle Cramps in Patients With Cirrhosis After 4 Weeks of Therapy [Baseline to end of 4 weeks of therapy]

   Patients undertook a muscle cramp questionnaire prior to treatment that measured severity in a 0-10 analog scale (0 is no pain and 10 is most severe pain). These measures were repeated after 4 weeks of therapy and the difference was assessed (4 weeks of therapy-Baseline).

3. Change in Frequency of Muscle Cramps After Washout Period [End of treatment (week 4) to end of washout (week 7)]

   Subjects undertook a muscle cramp questionnaire prior to treatment that measured frequency in the number of days in a week that a subject experienced muscle cramps and repeated this measure at the end of baclofen therapy (end of week 4). Subjects then underwent a 1 week taper of baclofen and a subsequent two week washout period. At the end of the washout period (end of week 7) the subjects underwent a final muscle cramp questionnaire to reassess frequency of muscle cramps. This was then compared to the end of therapy frequency to document the increase in muscle cramps after stopping baclofen. (week 7 result - week 4 result)

4. Change in Severity of Muscle Cramps After Washout Period [End of treatment (week 4) to end of washout (week 7)]

   Subjects undertook a muscle cramp questionnaire prior to treatment that measured severity on a 0-10 analog scale (0 is no pain, 10 is most severe pain) and repeated this measure at the end of baclofen therapy (end of week 4). Subjects then underwent a 1 week taper of baclofen and a subsequent two week washout period. At the end of the washout period (end of week 7) the subjects underwent a final muscle cramp questionnaire to reassess severity of muscle cramps. This was then compared to the end of therapy severity to document the increase in muscle cramps after stopping baclofen. (week 7 result - week 4 result)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Cirrhosis

• Presence of muscle cramps on a regular basis

Exclusion Criteria:

• Allergy or hypersensitivity to Baclofen

• Active or untreated Portosystemic encephalopathy

• Active alcohol or substance abuse

• Age less than 18

• Pregnancy

• Concomitant use of narcotic pain medication, other muscle relaxer, or other anti-spastic agent

• Concomitant use of Tricyclic Antidepressant due to drug interaction

• History of chronic kidney disease defined by GFR < 30 (using MDRD equation)

• Subject is institutionalized or a prisoner

• Inability or unwillingness to give informed consent

• Expected lifespan less than 3 months

• Severe or poorly controlled coexisting medical conditions or other significant issues as determined by the principal investigator to hinder the ability to adhere to study protocols

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Virginia

Investigators

• Principal Investigator: Zachary Henry, M.D., University of Virginia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zachary Henry, MD, Fellow Physician, University of Virginia
• ClinicalTrials.gov Identifier: NCT02298868
• Other Study ID Numbers: 16306
• First Posted: Nov 24, 2014
• Last Update Posted: Feb 5, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Muscle Cramp; Liver Cirrhosis; Spasm; Fibrosis; Baclofen

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Period Title: Overall Study
STARTED	10
COMPLETED	7
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Headache)
Description	Proportion of patients with headache at any time during the 4 weeks of therapy
Time Frame	4 weeks of active therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Number [participants]	3 30%

2. Secondary Outcome

Title	Efficacy of Baclofen to Change Frequency of Muscle Cramps in Patients With Cirrhosis at the End of 4 Weeks of Therapy
Description	Patients undertook a muscle cramp questionnaire prior to treatment that measured frequency in the number of days in a week that a subject experienced muscle cramps. This measures was repeated after 4 weeks of therapy and reported as the mean decrease in frequency of muscle cramps (4 weeks of therapy-Baseline).
Time Frame	Baseline to 4 weeks of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Mean (Standard Deviation) [days/week]	-4.4 (3.3)

3. Secondary Outcome

Title	Efficacy of Baclofen to Change Severity of Muscle Cramps in Patients With Cirrhosis After 4 Weeks of Therapy
Description	Patients undertook a muscle cramp questionnaire prior to treatment that measured severity in a 0-10 analog scale (0 is no pain and 10 is most severe pain). These measures were repeated after 4 weeks of therapy and the difference was assessed (4 weeks of therapy-Baseline).
Time Frame	Baseline to end of 4 weeks of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-6 (2.9)

4. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Nausea)
Description	Proportion of patients with nausea at any time during the 4 weeks of therapy
Time Frame	4 weeks of active therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Number [participants]	4 40%

5. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Dizziness)
Description	Proportion of patients with dizziness at any time during the 4 weeks of therapy
Time Frame	4 weeks of active therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Number [participants]	2 20%

6. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Encephalopathy)
Description	Proportion of patients with endephalopathy at any time during the 4 weeks of therapy
Time Frame	4 weeks of active therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Number [participants]	0 0%

7. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability (Somnolence)
Description	Proportion of patients with somnolence at any time during the 4 weeks of therapy
Time Frame	4 weeks of active therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Number [participants]	1 10%

8. Secondary Outcome

Title	Change in Frequency of Muscle Cramps After Washout Period
Description	Subjects undertook a muscle cramp questionnaire prior to treatment that measured frequency in the number of days in a week that a subject experienced muscle cramps and repeated this measure at the end of baclofen therapy (end of week 4). Subjects then underwent a 1 week taper of baclofen and a subsequent two week washout period. At the end of the washout period (end of week 7) the subjects underwent a final muscle cramp questionnaire to reassess frequency of muscle cramps. This was then compared to the end of therapy frequency to document the increase in muscle cramps after stopping baclofen. (week 7 result - week 4 result)
Time Frame	End of treatment (week 4) to end of washout (week 7)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Mean (Standard Deviation) [days/week]	3.0 (3.9)

9. Secondary Outcome

Title	Change in Severity of Muscle Cramps After Washout Period
Description	Subjects undertook a muscle cramp questionnaire prior to treatment that measured severity on a 0-10 analog scale (0 is no pain, 10 is most severe pain) and repeated this measure at the end of baclofen therapy (end of week 4). Subjects then underwent a 1 week taper of baclofen and a subsequent two week washout period. At the end of the washout period (end of week 7) the subjects underwent a final muscle cramp questionnaire to reassess severity of muscle cramps. This was then compared to the end of therapy severity to document the increase in muscle cramps after stopping baclofen. (week 7 result - week 4 result)
Time Frame	End of treatment (week 4) to end of washout (week 7)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	4.0 (4.0)

Adverse Events

Arm/Group Title	Treatment
Arm/Group Description	All patients will be administered a standing dose of Baclofen initially at 5 mg three times a day for the first week and then increased to 10 mg three times a day for the next 3 weeks with a tapering dose the final week, a total of 5 weeks of therapy.
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	6/10 (60%)
Gastrointestinal disorders
Nausea	4/10 (40%)
Nervous system disorders
Headache	3/10 (30%)
Dizziness	2/10 (20%)
Somnolence	1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.