Tamoxifen Treatment in Patients With Motor Neuron Disease

• ClinicalTrials.gov Identifier: NCT02166944
• Recruitment Status: Completed
• First Posted: June 18, 2014
• Last Update Posted: September 19, 2019
• Sponsor: Taipei Medical University Shuang Ho Hospital
• Information provided by (Responsible Party): Taipei Medical University Shuang Ho Hospital

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis; ALS Functional Ration Scale; TAR-DNA-binding Protein-43; Tamoxifen; mTOR	Drug: tamoxifen 40 mg daily for one year	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Study of Tamoxifen Treatment in Patients With Motor Neuron Disease
• Actual Study Start Date: April 2014
• Actual Primary Completion Date: September 17, 2019
• Actual Study Completion Date: September 18, 2019

Arms and Interventions

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 Name: Nolvadex
Placebo Comparator: placebo; placebo drugs	Drug: tamoxifen 40 mg daily for one year; both arms with riluzole daily; Other Name: Nolvadex

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) at 1, 3, 6,12 months [ Time Frame: Baseline, month 1, 3, 6, 12 ]
   Amyotrophic Lateral Sclerosis Functional Ration Scales (ALSFRS) measured by a neurologist

Secondary Outcome Measures :

1. Change from Baseline in pulmonary function test at 1, 3, 6,12 months [ Time Frame: 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 Outcome Measures:

1. Change from Baseline in blood TDP43 related biomarkers at 1, 3, 6,12 months [ Time Frame: baseline, month 1, 3, 6, 12 ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Taiwan

Po-Chih Chen

New Taipei City, Taiwan

Sponsors and Collaborators

Taipei Medical University Shuang Ho Hospital

Investigators

• Principal Investigator: Chaur-Jong Hu, M.D.; Shung Ho Hospital, Taipei Meidcal University

More Information

• Responsible Party: Taipei Medical University Shuang Ho Hospital
• ClinicalTrials.gov Identifier: NCT02166944
• Other Study ID Numbers: 201307022
• First Posted: June 18, 2014
• Last Update Posted: September 19, 2019
• Last Verified: June 2014

Keywords provided by Taipei Medical University Shuang Ho Hospital:

amyotrophic lateral sclerosis; ALS functional ration scale; TAR-DNA-binding protein-43; tamoxifen; mTOR

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Tamoxifen; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents