The NO-ALS Study: a Trial of Nicotinamide/pterostilbene Supplement in ALS.

Not Applicable

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)

• Registration Number: NCT04562831
• Lead Sponsor: Haukeland University Hospital

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a serious rapidly progressive disease of the nervous system. The average survival from the time of diagnosis is 3 years. Apart from Riluzole, there is no effective treatment. Care of advanced ALS will have a cost of 4-8 million NOK per year

Research i.a. from the investigators department has shown that increased activity in histone deacetylation enzymes (sirtuins) together with increased access to NAD can delay disease progression. Nicotinamide riboside (NR) can increase cells' access to NAD and Pterostilben will stimulate sirtuins.

The investigators want to study whether combination therapy with NR and Pterostilben can inhibit neurodegeneration in ALS and thereby delay disease development, increase survival and improve quality of life in ALS.

In the study, the investigators will use 2 different dosages on the active treatment and strength calculations show that 180 patients are needed to show a rather weak effect. Patients will be recruited in collaboration with hospitals in Helse Vest, AHUS, Drammen, OUS and St. Olavs hospital.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-18
• Study First Posted: 2020-09-24
• Study Start: 2020-10-07
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-02
• Primary Completion: 2025-08-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

Arm 1 (newly diagnosed ALS patients)

• Have a clinical diagnosis of probable ALS according to the revised El Escorial criteria.
• MR of the brain and cervical spine cannot explain symptoms.
• Diagnosed with likely ALS within 6 months from enrolment and treated with Riluzole 50mg x 2
• Symptom onset no longer than 2 year prior to inclusion.
• ALS-FRC-R of 36 or more (not any item below 2).
• Age equal to or greater than 35 years at time of enrollment

Arm 2 (earlier diagnosed ALS patients)

• Have a clinical diagnosis of probable ALS according to the revised El Escorial criteria.
• MR of the brain and cervical spine cannot explain symptoms.
• Treated with Riluzole 50mg x 2.

Exclusion Criteria

• Dementia, FTD or other neurodegenerative disorder at baseline visit
• Any psychiatric disorder that would interfere with compliance in the study.
• Use of high dose vitamin B3 supplementation within 30 days of enrollment
• Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
• Genetically confirmed mitochondrial disease
• Patients who become tracheostomized as part of the treatment of ALS
• Patients with short expected survival at the discretion of the investigator. Such cases cannot be expected to follow protocol procedures.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Newly diagnosed ALS patients	EH301 (Nicotinamide Riboside/Pterostilbene)	1. High dose EH301 (1500mg Nicotinamide riboside / 300mg Pterostilbene) 2. Single dose EH301 (1000mg Nicotinamide riboside / 200mg Pterostilbene) 3. Placebo
Earlier diagnosed ALS patients	EH301 (Nicotinamide Riboside/Pterostilbene)	1. High dose EH301 (1500mg Nicotinamide riboside / 300mg Pterostilbene) 2. Placebo

Primary Outcome Measures

Name	Time	Method
Disease progression as assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R)	Change from baseline to 1 year	ALSFRS-R is a validated rating instrument for monitoring the progression of disability in patients with ALS. The minimum score is 0 and the maximum score is 48, the higher score the more function is retained.

Secondary Outcome Measures

Name	Time	Method
Change in cognitive functions as assessed by the Edinburgh Cognitive Scale (ECAS)	Change from baseline to 1 year	ECAS determines cognitive and behavioural changes of patients suffering from ALS. The minimum score is 0 and the maximum score is 136, the lower the score the greater the deficit.
Change in vital capacity	Change from baseline to 1 year	Vital capacity in sitting position and supine by spirometry. Spirometry measures the amount of air that can be inhaled or exhaled and vital capacity is the volume of air breathed out after the deepest inhalation, the higher value the better vital capacity.
Change of Neurofilament light chain (NFL) levels in serum	Change from baseline to 1 year	NFL levels in serum, baseline values and changes during the study.
Change in quality of life as assessed by the quality of life questionnaire SF-36	Change from baseline to 1 year	SF-36 is a 36-item patient-reported survey of patient health. The minimum score is 0 and the maximum score is 100. The higher the score the less disability.

Trial Locations

Locations (9)

Haukeland University Hospital; 🇳🇴 Bergen, Norway

Vestre Viken HF; 🇳🇴 Drammen, Norway

Helse Førde HF; 🇳🇴 Førde, Norway

Helse Fonna HF; 🇳🇴 Haugesund, Norway

Akershus University Hospital; 🇳🇴 Lørenskog, Norway

Oslo University Hospital; 🇳🇴 Oslo, Norway

Stavanger University Hospital; 🇳🇴 Stavanger, Norway

Universitetssykehuset Nord-Norge; 🇳🇴 Tromsø, Norway

St.Olavs Hospital HF; 🇳🇴 Trondheim, Norway