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

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)

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.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumors (GISTs)
• Intervention / Treatment: Drug: L-carnitine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center, University of Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed GIST patients who are taking imatinib
2. Age 18years or older
3. Patients experienced muscle cramps for more than 8 times (pain of NRS > 4) or 4 times (pain of NRS >7) within last 4 weeks
4. Life expectancy > 6 months
5. ECOG performance status of 0-3

Exclusion Criteria:

1. Patients with renal disease receiving hemodialysis
2. Liver Cirrhosis patients with Child-Pugh class B or C
3. Patients with history of hypersensitivity to drugs including L-carnitine or nutritional supplements
4. Patients with history of spinal cord injury, peripheral vascular disease, or > Grade 2 peripheral sensory neuropathy
5. Patients with clinically significant electrolyte imbalances such as hypocalcemia, hypokalemia, and hypomagnesaemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: L-carnitine; L-carnitine 500mg three times daily (per oral)	Drug: L-carnitine; 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.
PLACEBO_COMPARATOR: Placebo; Placebo 500mg three times daily (per oral)	Drug: Placebo; Placebo 500mg TID(PO)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Hanmi Pharmaceutical Company Limited

Publications and helpful links

General Publications

• Chae H, Ryu MH, Ma J, Beck M, Kang YK. Impact of L-carnitine on imatinib-related muscle cramps in patients with gastrointestinal stromal tumor. Invest New Drugs. 2020 Apr;38(2):493-499. doi: 10.1007/s10637-019-00860-x. Epub 2019 Oct 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2018
• Primary Completion (ACTUAL): December 24, 2019
• Study Completion (ACTUAL): December 24, 2019

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (ACTUAL): February 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neurologic Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Spasm; Muscle Cramp
• Other Study ID Numbers: AMC1801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No