Effect of Nilotinib in Cerebellar Ataxia Patients

This is an institutional cohort study. Patients confirmed with spinocerebellar ataxia (SCA) and taking or planning to take Nilotinib (Tasigna®) are enrolled in this study. The daily dose of Nilotinib is 150mg-300mg and the patients will be followed up at 1, 3, 6, and 12 months. Rating scale for Friedreich's ataxia I and II and Barthel index are used as general function and daily living performance index. Scale for assessment and rating of ataxia (SARA) are used as an objective measure of cerebellar function. Adverse drug reactions are evaluated based on CTCAE version 4.0.

Study Overview

• Status: Completed
• Conditions: Ataxia, Cerebellar; Ataxia, Progressive
• Intervention / Treatment: Drug: Nilotinib

Detailed Description

1. Patients taking Nilotinib 1-1.Baseline information: demographics, genetic type of SCA, brain MRI, electrocardiography, routine blood evaluations 1-2. Time point of evaluation: At initiation of taking Nilotinib, 1, 3, 6, and 12 months 1-3. Evaluation items (at each time point) Routine check-up: electrocardiography, routine blood evaluations Adverse events: CTCAE version 4.0 Daily living performance: Barthel index General function: Friedreich's ataxia I and II 1-4. Change of drug dose Based on the attending physician's decision
2. Patients planning to take Nilotinib 2-1.Baseline information: demographics, genetic type of SCA, brain MRI, electrocardiography, routine blood evaluations 2-2. Time point of evaluation: Baseline, 1, 3, 6, and 12 months 2-3. Evaluation items (at each time point) Routine check-up: electrocardiography, routine blood evaluations Adverse events: CTCAE version 4.0 Cerebellar function: Scale for assessment and rating of ataxia (SARA) Daily living performance: Barthel index General function: Friedreich's ataxia I and II 2-4. Change of drug dose Based on the attending physician's decision

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed as chronic cerebellar ataxia
• Confirmed as spinocerebellar ataxia by gene test

Exclusion Criteria:

• Laboratory abnormalities that could interfere with the proper use of Nilotinib QTc interval >450ms on initial electrocardiograph, Hb <8.0, WBC<2000, ANC <1600, PLT <140,000, AST >200, ALT>200, ALP>575, Positive HIV serology, active hepatitis B
• Unstable mental or physical status that could interfere with precise evaluation and proper management of SCA Heart failure (NYHA Grade III or IV), history of major heart disease Pregnancy, on breast feeding

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: Nilotinib group; Patients with SCA and taking nilotinib treatment	Drug: Nilotinib; 150-300mg daily dose of nilotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activity of daily living	Barthel index: score range 0-6	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebellar function	Scale for the assessment and rating of ataxia (SARA): score range 0-36	12 month
General function	Rating scale for Friedreich's ataxia I: score range 0-6	12 month
Activity of daily living	Rating scale for Friedreich's ataxia II: score range 0-36	12 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events	CTCAE version 4.0	Baseline, 1 month, 3 month, 6 month, 12 month

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Publications and helpful links

General Publications

• Lee WJ, Moon J, Kim TJ, Jun JS, Lee HS, Ryu YJ, Lee ST, Jung KH, Park KI, Jung KY, Kim M, Lee SK, Chu K. The c-Abl inhibitor, nilotinib, as a potential therapeutic agent for chronic cerebellar ataxia. J Neuroimmunol. 2017 Aug 15;309:82-87. doi: 10.1016/j.jneuroim.2017.05.015. Epub 2017 May 24.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2018
• Primary Completion (Actual): August 13, 2020
• Study Completion (Actual): August 13, 2020

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: treatment; nilotinib; spinocerebellar ataxia; bcr-abl; receptor-tyrosine-kinase-inhibitor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Cerebellar Diseases; Ataxia; Cerebellar Ataxia
• Other Study ID Numbers: 1811-074-985

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The IPD will be provided upon request from any qualified investigator.

Drug and device information, study documents

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