L-carnitine vs Placebo for the Treatment of Muscle Cramps After Imatinib in Gastrointestinal Stromal Tumors

Study Overview
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Brief Summary
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we aim to evaluate the efficacy of L-carnitine for the treatment of muscle cramps after imatinib in patients with GIST and apply in the future.

Detailed Description
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One of the most common side effects of imatinib treatment, muscle cramps occur in about 30% of patients with gastrointestinal stromal tumor (GIST) receiving treatment with imatinib. It affects the quality of life (QoL) of patients and could also be a factor that affects compliance with treatment. Some studies suggest that L-carnitine may improve muscle cramps associated with cirrhosis or hemodialysis. However, the efficacy of L-carnitine for muscle cramps occurring after imatinib treatment has yet to be reported. Thus, we aim to evaluate the efficacy of L-carnitine for the treatment of muscle cramps after imatinib in patients with GIST and apply in the future.

Official Title
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Phase III Study of L-carnitine vs Placebo for the Treatment of Muscle Cramps After Imatinib in Patients With Gastrointestinal Stromal Tumors (GISTs) (Single-center Study)

Conditions
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Gastrointestinal Stromal Tumors (GISTs)

Intervention / Treatment
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* Drug: L-carnitine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed GIST patients who are taking imatinib Age 18years or older Patients experienced muscle cramps for more than 8 times (pain of NRS > 4) or 4 times (pain of NRS >7) within last 4 weeks Life expectancy > 6 months ECOG performance status of 0-3 Exclusion Criteria: Patients with renal disease receiving hemodialysis Liver Cirrhosis patients with Child-Pugh class B or C Patients with history of hypersensitivity to drugs including L-carnitine or nutritional supplements Patients with history of spinal cord injury, peripheral vascular disease, or > Grade 2 peripheral sensory neuropathy Patients with clinically significant electrolyte imbalances such as hypocalcemia, hypokalemia, and hypomagnesaemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: L-carnitine<br>L-carnitine 500mg three times daily (per oral) | Drug: L-carnitine<br>* L-carnitine VS Placebo is randomized (1:1) L-carnitine 500mg TID(PO), First evaluation will be performed at 8 weeks and then unblinding will be done. If symptoms continue after treatment, dose escalation in L-carnitine group by 1000mg TID (PO). If symptoms continue after treatment in Placebo group, L-carnitine 500mg TID(PO) will be given.<br>|
| Placebo Comparator: Placebo<br>Placebo 500mg three times daily (per oral) | Drug: Placebo<br>* Placebo 500mg TID(PO)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have occurrence of muscle cramps ( numeric rating scale score > 4) | Proportion of patients who have occurrence of muscle cramps ( numeric rating scale score > 4) decreased by less than 50% in 4 weeks excluding the first 4 weeks of drug administration *numeric rating scale scores(range, 0-10) -> higher score is worse outcome | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average numeric rating scale scores of muscle cramps | Change in average numeric rating scale scores(range, 0-10) of muscle cramps in 4 weeks excluding the first 4 weeks of drug administration *numeric rating scale scores(range, 0-10) -> higher score is worse outcome | 4 weeks | 
| Rate of patients who have duration of muscle cramps (numeric rating scale score > 4) | Rate of patients who have duration of muscle cramps (numeric rating scale score > 4) that was decreased by more than 50% in next 4 weeks excluding the first 4 weeks of drug administration *numeric rating scale scores(range, 0-10) -> higher score is worse outcome | 4 weeks | 
| questionnaire(Quality of Life) | Evaluation of the change in the Quality of Life in 4 weeks | 4 weeks | 
| plasma concentration level | Concentration evaluation of L-carnitine | 1 year | 
| recurrence rate | Recurrence is defined as 1) frequency of muscle cramps (NRS > 4) becomes more than 50% of baseline and 2) frequency of muscle cramps (NRS > 4) get twice worse than most improved time (when evaluated every 4 weeks) | 1 year |