Clinical trial NCT02166944: Tamoxifen Treatment in Patients With Motor Neuron Disease
Official title: The Study of Tamoxifen Treatment in Patients With Motor Neuron Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Taipei Medical University Shuang Ho Hospital
Sponsor class: OTHER
First posted: 2014-06-18
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) at 1, 3, 6,12 months
timeFrame: Baseline, month 1, 3, 6, 12
Secondary outcomes:
measure: Change from Baseline in pulmonary function test at 1, 3, 6,12 months
timeFrame: baseline, month 1, 3, 6, 12
Other outcomes:
measure: Change from Baseline in blood TDP43 related biomarkers at 1, 3, 6,12 months
timeFrame: baseline, month 1, 3, 6, 12
Locations:
city: New Taipei City
country: Taiwan
facility: Po-Chih Chen
Study officials:
affiliation: Shung Ho Hospital, Taipei Meidcal University
name: Chaur-Jong Hu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: