Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations

The study was designed as a single-center, open-label, single-arm pilot study to estimate the safety and efficacy L-carnitine in ALS patients with CHCHD10 mutations.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: L-Carnitine Injection，1000mg once daily

Detailed Description

The study was designed as a single-center, open-label, single-arm pilot study and was performed at the ALS inpatient clinic of the Xuanwu Hospital in Beijing, China. ALS patients with CHCHD10 mutations were recruited to participate in the clinical trial. The patients were given L-carnitine therapy administered every 8 weeks, consisting of 1g L-carnitine diluted in 500 mL of 0.9% sodium chloride solution via intravenous infusion once daily. Each treatment cycle lasted 2 weeks, repeated at 8-week intervals for a total of 3 cycles, with L-carnitine 1g is administered orally once daily during the intervals between intravenous therapies. Primary end point was the changes of ALS-FRS-R scores, and secondary end points were the changes of plasm NfL level, FVC%, weight and ALSAQ-40 scores. Eligible patients were assessed at baseline and after 2, 10, 12, 20 and 30 weeks. At each visit, a detailed neurological examination, including assessment of general nerve function as well as quantitative and qualitative evaluation of the motor system, were performed for the patients. All adverse events (AEs) encountered and any serious events were to be recorded as true. Severity was graded according to the modified WHO criteria for toxicity (http://www.regsource. com/_Adverse_Event_Reporting/_adverse_event_ reporting.html) where applicable.

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

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, 18-80 years old
• ALS diagnosed as definite or probable as defined by the World Federation of Neurology revised El Escorial criteria
• Carrying pathogenic CHCHD10 mutations
• Capable of providing informed consent and following trial procedures
• Forced Vital Capacity (FVC) >40% of predicted value for gender, height, and age at the Screening Visit
• Subjects develop at less moderate degree of motor dysfunction, with ALS-FRS-R total scores less than 46
• Both male and female patients must agree to use adequate birth control for the whole duration of the study within 30 weeks
• Subjects are willing and expected to complete the 30-week follow up, including 3 times hospitalization.

Exclusion Criteria:

• Presence of tracheostomy
• History of known allergy to L-carnitine
• Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal
• Renal insufficiency as defined by eGFR < 60 mL/min/1.73m2
• Pregnant women or women currently breastfeeding
• Clinically significant unstable medical condition (other than ALS) that would pose a risk to the subject if they were to participate in the study
• Anything that, in the opinion of the Site Investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: L-carnitine group

Drug: L-Carnitine Injection，1000mg once daily; All patients were given L-carnitine therapy administered every 8 weeks, consisting of 1g L-carnitine diluted in 500 mL of 0.9% sodium chloride solution via intravenous infusion once daily. Each treatment cycle lasted 2 weeks, repeated at 8-week intervals for a total of 3 cycles, with L-carnitine 1g is administered orally once daily during the intervals between intravenous therapies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of ALS-FRS-R scores	ALS-Functional Rating Scale-Revised (ALS-FRS-R) score ranges from 0 to 48, with higher scores indicating better motor function (0 = complete loss of motor function; 48 = intact/normal motor function)	Eligible patients were assessed at baseline and after 2, 10, 12, 20 and 30 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of plasm NfL level		Eligible patients were assessed at baseline and after 10, 20 and 30 weeks.
Changes of FVC%	Predicted forced vital capacity (FVC)%	Eligible patients were assessed at baseline and after 10, 20 and 30 weeks.
Changes of Weight		Eligible patients were assessed at baseline and after 2, 10, 12, 20 and 30 weeks.
Changes of ALSAQ-40 scores	The Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) total scores range from 0 to 120. Higher scores indicate greater disease burden or poorer quality of life.	Eligible patients were assessed at baseline and after 2, 10, 12, 20 and 30 weeks.

Collaborators and Investigators

• Sponsor: ChaodongWang

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Actual): December 19, 2024
• Study Completion (Actual): February 13, 2025

Study Registration Dates

• First Submitted: February 23, 2025
• First Submitted That Met QC Criteria: February 23, 2025
• First Posted (Actual): February 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; L-carnitine; CHCHD10; flail arm syndrome
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: ALS-L-carnitine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No