UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000026150
Receipt number R000028606
Scientific Title Safety and efficacy of mexiletine hydrochroride in spinal and bulbar muscular atrophy (SBMA) :a multicenter, randomised, double-blind, placebo-controlled trial
Date of disclosure of the study information 2017/03/31
Last modified on 2023/02/06 10:00:21

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Basic information

Public title

Safety and efficacy of mexiletine hydrochroride in spinal and bulbar muscular atrophy (SBMA) :a multicenter, randomised, double-blind, placebo-controlled trial

Acronym

Mexiletine in SBMA

Scientific Title

Safety and efficacy of mexiletine hydrochroride in spinal and bulbar muscular atrophy (SBMA) :a multicenter, randomised, double-blind, placebo-controlled trial

Scientific Title:Acronym

Mexiletine in SBMA

Region

Japan


Condition

Condition

Spinal and Bulbar Muscular Atrophy

Classification by specialty

Medicine in general Neurology

Classification by malignancy

Others

Genomic information

YES


Objectives

Narrative objectives1

To evaluate efficacy and safety of mexiletine hydrochrolide in the patients with SBMA

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase II


Assessment

Primary outcomes

Change of the difference in distal latencies between under room temperature and cold exposure at 4 weeks

Key secondary outcomes

(1)Quantitative muscle strength of upper limbs (grip power, pinch power, ten seconds test)
(2)Peripheral nerve conduction studies (distal latency, compound muscle action potential, motor nerve conduction velocity, sensory nerve conduction velocity, area, duration time, Harvey-Masland test, skin temperature)
(3)Motor function test (tongue pressure, timed walk test, modified QMG score)
(4)Pulmonary function test (vital capacity, forced vital capacity, forced expiratory volume, peak expiratory flow and V50/V25, flow-volume curve)
(5)ADL scales (ALSFRS-R, SBMAFRS)
(6)QOL scales (36-Item Short Form Health Survey, The Individualised Neuromuscular Quality of Life questionnaire, Interactive Voice Response System)
(7)Lean mass evaluation by Dual-energy X-ray Absorption
(8)Blood examinations (creatine kinase, aldolase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, testosterone)


Base

Study type

Interventional


Study design

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Mexiletine Hydrochloride 300mg daily, for 4 weeks

Interventions/Control_2

placebo for 4 weeks

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

80 years-old >=

Gender

Male

Key inclusion criteria

1. Male Patients whose number of the CAG repeat in the androgen receptor gene is 38 or more
2. Patients with muscle weakness due to lower motor neuronal loss (bulbar palsy or extremity palsy)
3. Patients with muscle weakness or myotonia under cold exposure
4. Patients are between 20 and 80 years old at the time of the agreement acquisition
5. Patients who are capable of ambulatory hospital visits
6. Patients whose hepatic and renal functions meet the following criteria:
Serum AST,ALT: <4.0 * Upper Limit of Institutional Reference Value
Serum creatinine: <1.5 * Upper Limit of Institutional Reference Value
7. Patients with written informed consent

Key exclusion criteria

1. Patients who have hypersensitivity for this medicine
2. Patients who have second degree atrioventricular block, third degree atrioventricular block, or left bundle branch block
3. Patients who show Brugada-type ECG
4. Patients who have past history of myocardial infarction, valvular disease, or cardiomyopathy
5. Patients whose heart rate is 50 /min or less
6. Patients who have severe liver or renal dysfunction
7. Patients who have heart failure
8. Patients whose systolic blood pressure is 90mmHg or less
9. Patients who have parkinsonism
10. Patients whose serum potassium level is 3.5mEq/l or less
11. Patients who take anti-arrhythmic drug
12. Patients who take anti-epileptic drug
13. Patient who have neurological disorders except for SBMA
14. Patients whose HbA1c(NGSP) level is 6.5% or more
15. Patients who take hypoglycemic drugs
16. Patients who are alcohol addicts
17. Patients who are drug addicts
18. Patients who take cimetidine, rifampicin, or theophylline
19. Patients who have severe complication
20. Patients whose grip power of dominant hand is less than 10kg
21. Patients who are judged to be inappropriate to participate in the trial by any other reasons

Target sample size

20


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Masahisa Katsuno

Organization

Nagoya University Graduate School of Medicine

Division name

Department of Neurology

Zip code


Address

65 Tsurumai-cho, Showa-ku, Nagoya city 466-8550, Japan

TEL

052-744-2385

Email

ka2no@med.nagoya-u.ac.jp


Public contact

Name of contact person

1st name
Middle name
Last name Shinichiro Yamada

Organization

Nagoya University Graduate School of Medicine

Division name

Neurology

Zip code


Address

65 Tsurumai-cho, Showa-ku, Nagoya city 466-8550, Japan

TEL

052-744-2390

Homepage URL


Email

s.yamada@med.nagoya-u.ac.jp


Sponsor or person

Institute

Nagoya University Graduate School of Medicine

Institute

Department

Personal name



Funding Source

Organization

Japan Society for the Promotion of Science

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization


Address


Tel


Email



Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions



Other administrative information

Date of disclosure of the study information

2017 Year 03 Month 31 Day


Related information

URL releasing protocol

https://pubmed.ncbi.nlm.nih.gov/30206090/

Publication of results

Published


Result

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/36208052/

Number of participants that the trial has enrolled

20

Results

In the MEXPRESS trial, 20 participants took mexiletine or lactose, three times a day for 4 weeks with a crossover design. There was no difference in distal latencies at room temperature and under cold exposure between mexiletine and placebo groups as the primary endpoint. However, tongue pressure and 10-sec grip and release test under cold exposure were improved in the mexiletine group. There were no serious adverse events throughout the study period.

Results date posted

2023 Year 02 Month 06 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

We assessed 20 patients with SBMA. The mean CAG repeat length was 48.4. The baseline characteristics of the two groups were similar. However, more patients were treated with leuprorelin acetate in the mexiletine group than in the placebo group.

Participant flow

From April 2017 through June 2018, 22 patients with SBMA were assessed for eligibility. We excluded two patients due to Brugada-type patterns on electrocardiogram. A final total of 20 patients were enrolled and randomly assigned to receive either mexiletine or placebo. The first patient was enrolled on August 17, 2017. None of the patients dropped out during the clinical trial period, and all patients were included in the full analysis set.

Adverse events

There were no serious adverse events in participants.

Outcome measures

There was no significant difference in distal latencies at room temperature and under cold exposure conditions as the primary endpoint between the mexiletine and placebo groups. ALSFRS-R was improved in the mexiletine group, but this was not statistically different from the placebo group. Values obtained in quantitative motor function tests such as tongue pressure and 10-sec grip and release, which are key clinical indices in patients with SBMA, were improved in the mexiletine group. Although grip strength, timed walk, and respiratory function tests were improved in the mexiletine group, these values were not statistically different from those in the placebo group. Mexiletine also improved body pain based on patient reports of pain severity scores (treatment effect estimate, 0.53; 95% confidence interval [CI], 1.02 to 0.04; p = 0.035) and subscales of SF-36 (treatment effect estimate, 6.39; 95% CI, 0.65 to 12.13; p = 0.031). To evaluate the carryover and period effects, results with participant differences are presented separately for each period (Table S4). We did not observe a period effect in this trial.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2017 Year 02 Month 22 Day

Date of IRB

2017 Year 03 Month 31 Day

Anticipated trial start date

2017 Year 04 Month 25 Day

Last follow-up date

2018 Year 06 Month 14 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information



Management information

Registered date

2017 Year 02 Month 15 Day

Last modified on

2023 Year 02 Month 06 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028606


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name