Tamoxifen Treatment in Patients With Motor Neuron Disease

The Study of Tamoxifen Treatment in Patients With Motor Neuron Disease

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • New Taipei City, Taiwan
    • Po-Chih Chen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tamoxifen; tamoxifen 40 mg daily for one year	Drug: tamoxifen 40 mg daily for one year; both arms with riluzole daily; Other Names: Nolvadex
Placebo Comparator: placebo; placebo drugs	Drug: tamoxifen 40 mg daily for one year; both arms with riluzole daily; Other Names: Nolvadex

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in pulmonary function test at 1, 3, 6,12 months	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)	baseline, month 1, 3, 6, 12

Other Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in blood TDP43 related biomarkers at 1, 3, 6,12 months	baseline, month 1, 3, 6, 12

Collaborators and Investigators

• Sponsor: Taipei Medical University Shuang Ho Hospital
• Investigators: Principal Investigator: Chaur-Jong Hu, M.D., Shung Ho Hospital, Taipei Meidcal University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): September 18, 2019

Study Registration Dates

• First Submitted: June 9, 2014
• First Submitted That Met QC Criteria: June 16, 2014
• First Posted (Estimate): June 18, 2014

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: tamoxifen; amyotrophic lateral sclerosis; mTOR; ALS functional ration scale; TAR-DNA-binding protein-43
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: 201307022