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

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 mean survival from the time of diagnosis is 2.5 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 NO-ALS extension study the investigators will follow the patients who completed the original NO-ALS study. Objectives are to evaluate adverse events and give patients possibility of compassionate use, and secondarily to see if EH301 will decrease progression of motor symptoms and loss of vital capacity, and increase survival time in patients with ALS.

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

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: Patients who fulfilled the criteria for the NO-ALS study and have completed the study will be proposed inclusion in the NO-ALS extension study protocol. Patients from both arm 1 and arm 2 in the NO-ALS study will be allowed inclusion in the prolongation study Exclusion Criteria: Individuals will be excluded if any of the following exclusion criteria apply: Dementia, FTD or other neurodegenerative disorder interfereing with compliance. Metabolic, neoplastic, or other physically or mentally debilitating disorder. 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. Use of Vit B3 or blue berry extracts outside the study

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
Intervention Model: Single Group Assignment
Interventional Model Description: The study is a multicenter open label study as a follow up of the NO-ALS trial. Newly diagnosed ALS cases were included in the study arm 1. Earlier ALS cases were included in study arm 2 to allow patients with earlier ALS to participate in the study as the treatment options outside the study were limited. The NO-ALS study will be stopped when we reach 180 patients in the group with newly diagnosed ALS cases (arm 1). This is the follow up study for pasients completing 1 year follow up in the NO-ALS study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: NO-ALS Extension Study High Dose EH301<br> | Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)<br>* For this study EH301 is defined as Investigational Product(s) (IP). The ALS extension study is an open label study with active treatment of all patients thet have passed through the NO-ALS trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Studies of adverse events including changes in lab parameters induced by high dose oral NR/pterostilbene. | Through study completion, 1 year | 

Secondary 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. | Determined after 12 months of follow-up. | 
| Change in vital capacity | Vital capacity measured by spirometry. | Determined after 12 months of follow-up. |