Tamoxifen Treatment in Patients With Motor Neuron Disease

Phase 1

Completed

• Conditions: Tamoxifen; Amyotrophic Lateral Sclerosis; ALS Functional Ration Scale; TAR-DNA-binding Protein-43; mTOR
• Interventions: Drug: tamoxifen 40 mg daily for one year

• Registration Number: NCT02166944
• Lead Sponsor: Taipei Medical University Shuang Ho Hospital

Brief Summary

The aim of this study is to survey the effect of Tamoxifen in motor neuron disease (MND) patients, amyotrophic lateral sclerosis (ALS) with regular riluzole usage. TDP-43 is related to ALS. Increased the ubiquitinated or phosphorylated TDP-43 can cause animal model of ALS, and TDP43 can be degraded either by proteasome or autophagy pathway system. Autophagy pathway can be activated by mTOR inhibition, resulting in ameliorating TDP-43 accumulation and rescue in motor function in animal model. Tamoxifen had shown ability of enhance both proteasome and autophagy pathway, therefore the investigators assume that Tamoxifen probably can ameliorate TDP-43 accumulation and inclusion body formation in ALS.

Detailed Description

The investigators will assess the ALSFR-s in ALS patients at start, 1, 3, 6 and 12 months and correlate the score to the neurological outcome of the patients with and without tamoxifen treatment at dose of 40mg daily for one year.

The study will be able to prove the investigators hypothesis: Tamoxifen, a protease and autophagy enhancer, has synergic effect with riluzole in ALS patients to slowing the progression of neurological dysfunction, and respiratory insufficiency.

Study Timeline

• Study Start: 2014-04
• Status Verified: 2014-06
• Study First Submitted: 2014-06-09
• Study First Submitted QC: 2014-06-16
• Study First Posted: 2014-06-18
• Primary Completion: 2019-09-17
• Last Update Submitted: 2019-09-17
• Study Completion: 2019-09-18
• Last Update Posted: 2019-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Clinical diagnosed and confirmed ALS patients, with regular follow up and oral form riluzole at National Taiwan University or Shuang- Ho Hospital for more than 6 months.
2. Age ≧20 years old

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Exclusion Criteria

1. Patients who had already ventilator dependent, not regular followed up for more than 6 months or against medical advice, refuse to follow up at neurology department will be excluded in this study.
2. Patients with now or previous usage of Tamoxifen
3. Patients with any contraindications of Tamoxifen usage
4. Patients with other internal medicine illiness

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
tamoxifen	tamoxifen 40 mg daily for one year	tamoxifen 40 mg daily for one year
placebo	tamoxifen 40 mg daily for one year	placebo drugs

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) at 1, 3, 6,12 months	Baseline, month 1, 3, 6, 12	Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) measured by a neurologist

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in pulmonary function test at 1, 3, 6,12 months	baseline, month 1, 3, 6, 12	Expiratory reserve volume (ERV) Forced vital capacity (FVC) Forced expiratory volume (FEV) Forced expiratory flow 25% to 75% Functional residual capacity (FRC) Maximum voluntary ventilation (MVV); * Residual volume (RV); * Peak expiratory flow (PEF).; * Slow vital capacity (SVC); * Total lung capacity (TLC)

Trial Locations

Locations (1)

Po-Chih Chen; 🇨🇳 New Taipei City, Taiwan