Levocarnitine in Treating Patients With Vismodegib-Associated Muscle Spasms

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

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.

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

Conditions
-----------------
Musculoskeletal Complications

Intervention / Treatment
-----------------
* Dietary Supplement: levocarnitine
* Other: placebo
* Other: questionnaire administration


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Basal Cell Carcinoma, Gorlin syndrome, Erivedge, Basal Cell Nevus Syndrome