ALS Functional Ration Scale, Amyotrophic Lateral Sclerosis, mTOR, Tamoxifen, TAR-DNA-binding Protein-43
Conditions
Keywords
amyotrophic lateral sclerosis, ALS functional ration scale, TAR-DNA-binding protein-43, tamoxifen, mTOR
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.
Interventions
DRUGtamoxifen 40 mg daily for one year
both arms with riluzole daily
Sponsors
Taipei Medical University Shuang Ho Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Other
| Measure | Time frame |
|---|---|
| Change from Baseline in blood TDP43 related biomarkers at 1, 3, 6,12 months | baseline, month 1, 3, 6, 12 |
Countries
Taiwan
Outcome results
None listed