Levocarnitine in Treating Patients With Vismodegib-Associated Muscle Spasms

Double-blind, Randomized, Placebo-controlled Two-period Crossover Study to Assess the Effect of Levocarnitine on Vismodegib-associated Muscle Spasms

This randomized clinical trial studies levocarnitine in treating patients with vismodegib-associated muscle spasms. Levocarnitine may decrease muscle spasms caused by vismodegib.

Study Overview

• Status: Completed
• Conditions: Musculoskeletal Complications
• Intervention / Treatment: Other: questionnaire administration; Other: placebo; Dietary supplement: levocarnitine

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the effect of levocarnitine on muscle spasm frequency compared to placebo (median percentage comparison)

SECONDARY OBJECTIVES:

I. To assess intensity of muscle spasms after levocarnitine compared to placebo.

II. To assess responses related to activities of daily living or psychosocial function after levocarnitine compared to placebo.

III. To assess the number of body locations affected by muscle spasms after levocarnitine or placebo.

IV. To assess the frequency and severity of all adverse effects on levocarnitine versus placebo.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive levocarnitine orally (PO) twice daily (BID) during weeks 1-4. Washout is from weeks 5-8. Patients then cross-over to placebo PO twice daipy for weeks 9-12.

ARM II: Patients receive placebo PO twice daily during weeks 1-4. Washout is from weeks 5-8. Patients then cross-over to levocarnitine for weeks 9-12.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Taking vismodegib daily
• Subject answers item #1 of muscle spasms questionnaire as moderate or severe intensity at time of screening
• At least one muscle spasm per day at time of screening
• Muscle spasms onset after starting vismodegib
• Willing and able to understand and sign consent form

Exclusion Criteria:

• Presence of muscle spasms or active neurologic disease prior to start of vismodegib
• Use of thyroid medication at the time of screening
• Use of Coumadin or acenocoumarol at time of screening
• Change in regimen of muscle relaxant medications within four weeks of enrollment
• If on stable muscle relaxant medication regimen for 4 weeks prior to enrolling, not willing to maintain muscle relaxant regimen without change during course of the study
• Presence of significant renal disease or hemodialysis which would result in dramatic reductions of systemic levocarnitine levels
• History of seizures
• Known deficiency in carnitine (genetic, etc.)
• Any uncontrolled medical condition which may place the patient at increased risk during study participation (at the discretion of the clinical investigator)
• Unable or unwilling to comply with study procedures
• Pregnant or lactating
• All female patients of childbearing potential including those who are within 1 year of last menstrual period will be required to take a pregnancy test during screening, enrollment and at week 0, 4, 8 and 12
• If female of reproductive age, or male partner of female of reproductive age, unwilling to use two medically reliable forms of birth control while on vismodegib
• Unwilling to refrain from donation of bodily fluid (blood, platelets, etc.) within 7 months of last vismodegib dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (levocarnitine start); Patients receive levocarnitine PO BID during weeks 1-4. Washout is weeks 5-8. Patients then cross-over to placebo for weeks 9-12.	Other: questionnaire administration; Ancillary studies; Dietary supplement: levocarnitine; Given PO; Other Names: L-carnitine; Carnitor
Placebo Comparator: Arm II (placebo start); Patients receive placebo PO BID during weeks 1-4. Washout is weeks 5-8. Patients then cross-over to levocarnitine for weeks 9-12.	Other: questionnaire administration; Ancillary studies; Other: placebo; Given PO; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage difference in muscle spasm frequency (defined as number per week) between levocarnitine and placebo	Wilcoxon rank-sum test, paired	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in severity of muscle spasms after levocarnitine and placebo	Wilcoxon rank-sum test, paired	12 weeks
Change in number of body locations affected by muscle spasms after levocarnitine and placebo	Wilcoxon rank-sum test, paired	12 weeks
Change in impact of spasms on activities of daily living (such as sleeping or driving) after levocarnitine and placebo	as measured on questionnaire items	12 weeks
Social/emotional impacts of muscle spasms after levocarnitine and placebo	as measured on questionnaire items	12 weeks
Frequency of adverse events after levocarnitine and placebo	according to CTCAE 4.03	12 weeks
Severity of adverse events after levocarnitine and placebo	according to CTCAE 4.03	12 weeks

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anne Lynn Chang, Stanford University

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): March 15, 2017
• Study Completion (Actual): March 15, 2017

Study Registration Dates

• First Submitted: July 2, 2013
• First Submitted That Met QC Criteria: July 2, 2013
• First Posted (Estimate): July 9, 2013

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Basal Cell Nevus Syndrome; Basal Cell Carcinoma; Gorlin syndrome; Erivedge
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Spasm
• Other Study ID Numbers: SKIN0018; P30CA124435 (U.S. NIH Grant/Contract); NCI-2013-01269 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 27478