The NO-ALS Study: A Trial of Nicotinamide/Pterostilbene Supplement in ALS.

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Placebo-controlled Trial of Nicotinamide/Pterostilbene Supplement in ALS: The NO-ALS Study

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Newly diagnosed ALS patients<br>High dose EH301 (1500mg Nicotinamide riboside / 300mg Pterostilbene) Single dose EH301 (1000mg Nicotinamide riboside / 200mg Pterostilbene) Placebo | Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)<br>* Comparison of 2 different dosages with placebo in newly diagnosed ALS patients and comparison of high dose with placebo in earlier ALS patients.<br>|
| Experimental: Earlier diagnosed ALS patients<br>High dose EH301 (1500mg Nicotinamide riboside / 300mg Pterostilbene) Placebo | Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)<br>* Comparison of 2 different dosages with placebo in newly diagnosed ALS patients and comparison of high dose with placebo in earlier ALS patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression as assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) | 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. | Change from baseline to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vital capacity | 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 from baseline to 1 year | 
| Change in cognitive functions as assessed by the Edinburgh Cognitive Scale (ECAS) | 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 from baseline to 1 year | 
| Change of Neurofilament light chain (NFL) levels in serum | NFL levels in serum, baseline values and changes during the study. | Change from baseline to 1 year | 
| Change in quality of life as assessed by the quality of life questionnaire SF-36 | 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. | Change from baseline to 1 year |