Tamoxifen Treatment in Patients With Motor Neuron Disease
Primary Purpose
Amyotrophic Lateral Sclerosis, ALS Functional Ration Scale, TAR-DNA-binding Protein-43
Status
Completed
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
tamoxifen 40 mg daily for one year
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring amyotrophic lateral sclerosis, ALS functional ration scale, TAR-DNA-binding protein-43, tamoxifen, mTOR
Eligibility Criteria
Inclusion Criteria:
- 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.
- Age ≧20 years old
Exclusion Criteria:
- 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.
- Patients with now or previous usage of Tamoxifen
- Patients with any contraindications of Tamoxifen usage
- Patients with other internal medicine illiness
Sites / Locations
- Po-Chih Chen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
tamoxifen
placebo
Arm Description
tamoxifen 40 mg daily for one year
placebo drugs
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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)
Full Information
NCT ID
NCT02166944
First Posted
June 9, 2014
Last Updated
September 17, 2019
Sponsor
Taipei Medical University Shuang Ho Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02166944
Brief Title
Tamoxifen Treatment in Patients With Motor Neuron Disease
Official Title
The Study of Tamoxifen Treatment in Patients With Motor Neuron Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
September 17, 2019 (Actual)
Study Completion Date
September 18, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taipei Medical University Shuang Ho Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis, ALS Functional Ration Scale, TAR-DNA-binding Protein-43, Tamoxifen, mTOR
Keywords
amyotrophic lateral sclerosis, ALS functional ration scale, TAR-DNA-binding protein-43, tamoxifen, mTOR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
tamoxifen
Arm Type
Experimental
Arm Description
tamoxifen 40 mg daily for one year
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo drugs
Intervention Type
Drug
Intervention Name(s)
tamoxifen 40 mg daily for one year
Other Intervention Name(s)
Nolvadex
Intervention Description
both arms with riluzole daily
Primary Outcome Measure Information:
Title
Change from Baseline in Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) at 1, 3, 6,12 months
Description
Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) measured by a neurologist
Time Frame
Baseline, month 1, 3, 6, 12
Secondary Outcome Measure Information:
Title
Change from Baseline in pulmonary function test at 1, 3, 6,12 months
Description
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)
Time Frame
baseline, month 1, 3, 6, 12
Other Pre-specified Outcome Measures:
Title
Change from Baseline in blood TDP43 related biomarkers at 1, 3, 6,12 months
Time Frame
baseline, month 1, 3, 6, 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Age ≧20 years old
Exclusion Criteria:
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.
Patients with now or previous usage of Tamoxifen
Patients with any contraindications of Tamoxifen usage
Patients with other internal medicine illiness
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chaur-Jong Hu, M.D.
Organizational Affiliation
Shung Ho Hospital, Taipei Meidcal University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Po-Chih Chen
City
New Taipei City
Country
Taiwan
12. IPD Sharing Statement
Learn more about this trial
Tamoxifen Treatment in Patients With Motor Neuron Disease
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