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

• ClinicalTrials.gov Identifier: NCT04562831
• Recruitment Status: Recruiting
• First Posted: September 24, 2020
• Last Update Posted: September 25, 2023
• Sponsor: Haukeland University Hospital
• Collaborator: Elysium Health
• Information provided by (Responsible Party): Haukeland University Hospital

Tracking Information

• First Submitted Date: September 10, 2020
• First Posted Date: September 24, 2020
• Last Update Posted Date: September 25, 2023
• Actual Study Start Date: October 7, 2020
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2020)

Disease progression as assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 18, 2020)

• Change in vital capacity [ Time Frame: 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 in cognitive functions as assessed by the Edinburgh Cognitive Scale (ECAS) [ Time Frame: 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 of Neurofilament light chain (NFL) levels in serum [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 18, 2020)

Overall survival [ Time Frame: Through study completion, 1 year ]

Survival of patients through the study

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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 Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)

Comparison of 2 different dosages with placebo in newly diagnosed ALS patients and comparison of high dose with placebo in earlier ALS patients.

Study Arms

• Experimental: Newly diagnosed ALS patients
  1. High dose EH301 (1500mg Nicotinamide riboside / 300mg Pterostilbene)
  2. Single dose EH301 (1000mg Nicotinamide riboside / 200mg Pterostilbene)
  3. Placebo
  Intervention: Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)
• Experimental: Earlier diagnosed ALS patients
  1. High dose EH301 (1500mg Nicotinamide riboside / 300mg Pterostilbene)
  2. Placebo
  Intervention: Dietary Supplement: EH301 (Nicotinamide Riboside/Pterostilbene)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 18, 2020): 380
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2025
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ole-Bjørn Tysnes; +4755975063; obty@haukeland.no

• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT04562831
• Other Study ID Numbers: 98955
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Haukeland University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Haukeland University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Elysium Health

Investigators

• Principal Investigator: Ole-Bjørn Tysnes; Haukeland University Hospital

• PRS Account: Haukeland University Hospital
• Verification Date: September 2023