Unique ID issued by UMIN | UMIN000026150 |
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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 |
Safety and efficacy of mexiletine hydrochroride in spinal and bulbar muscular atrophy (SBMA) :a multicenter, randomised, double-blind, placebo-controlled trial
Mexiletine in SBMA
Safety and efficacy of mexiletine hydrochroride in spinal and bulbar muscular atrophy (SBMA) :a multicenter, randomised, double-blind, placebo-controlled trial
Mexiletine in SBMA
Japan |
Spinal and Bulbar Muscular Atrophy
Medicine in general | Neurology |
Others
YES
To evaluate efficacy and safety of mexiletine hydrochrolide in the patients with SBMA
Safety,Efficacy
Exploratory
Explanatory
Phase II
Change of the difference in distal latencies between under room temperature and cold exposure at 4 weeks
(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)
Interventional
Cross-over
Randomized
Individual
Double blind -all involved are blinded
Placebo
2
Treatment
Medicine |
Mexiletine Hydrochloride 300mg daily, for 4 weeks
placebo for 4 weeks
20 | years-old | <= |
80 | years-old | >= |
Male
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
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
20
1st name | |
Middle name | |
Last name | Masahisa Katsuno |
Nagoya University Graduate School of Medicine
Department of Neurology
65 Tsurumai-cho, Showa-ku, Nagoya city 466-8550, Japan
052-744-2385
ka2no@med.nagoya-u.ac.jp
1st name | |
Middle name | |
Last name | Shinichiro Yamada |
Nagoya University Graduate School of Medicine
Neurology
65 Tsurumai-cho, Showa-ku, Nagoya city 466-8550, Japan
052-744-2390
s.yamada@med.nagoya-u.ac.jp
Nagoya University Graduate School of Medicine
Japan Society for the Promotion of Science
Other
NO
2017 | Year | 03 | Month | 31 | Day |
https://pubmed.ncbi.nlm.nih.gov/30206090/
Published
https://pubmed.ncbi.nlm.nih.gov/36208052/
20
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.
2023 | Year | 02 | Month | 06 | Day |
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.
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.
There were no serious adverse events in participants.
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.
Completed
2017 | Year | 02 | Month | 22 | Day |
2017 | Year | 03 | Month | 31 | Day |
2017 | Year | 04 | Month | 25 | Day |
2018 | Year | 06 | Month | 14 | Day |
2017 | Year | 02 | Month | 15 | Day |
2023 | Year | 02 | Month | 06 | Day |
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028606
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