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

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

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 (Norwegian kroner) per year.

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

The investigators want to study whether combination therapy with NR and Pterostilbene 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 the combination of NR and pterostilbene (EH301) will decrease progression of motor symptoms and loss of vital capacity, and increase survival time in patients with ALS.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Dietary supplement: EH301 (Nicotinamide Riboside/Pterostilbene)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ole-Bjørn Tysnes; Phone Number: +4755975063; Email: obty@haukeland.no

Study Locations

• Norway
  • Bergen, Norway
    • Recruiting
    • Haukeland University Hospital
    • Contact: Ole-Bjørn Tysnes; Phone Number: +4755975063/+4790686700; Email: obty@haukeland.no
    • Principal Investigator: Ole-Bjørn Tysnes
  • Bodø, Norway
    • Not yet recruiting
    • Nordlandssykehuset HF
    • Contact: Espen Benjaminsen; Phone Number: +4748103893; Email: Espen.Benjaminsen@nordlandssykehuset.no
    • Principal Investigator: Espen Benjaminsen
  • Drammen, Norway
    • Not yet recruiting
    • Vestre Viken HF
    • Contact: Ingrid Kristine Bjørnå; Phone Number: +4741339297; Email: Ingrid.Kristine.Bjorna@vestreviken.no
    • Principal Investigator: Ingrid Kristine Bjørnå
  • Førde, Norway
    • Not yet recruiting
    • Helse Førde HF
    • Contact: Kristin Lif Breivik; Phone Number: +4793630457; Email: kristin.lif.breivik@helse-forde.no
    • Principal Investigator: Kristin Lif Breivik
  • Haugesund, Norway
    • Not yet recruiting
    • Helse Fonna HF
    • Contact: Ineke HogenEsch; Phone Number: +4752732590; Email: ineke.hogenesch@helse-fonna.no
    • Principal Investigator: Ineke HogenEsch
  • Kristiansand, Norway
    • Not yet recruiting
    • Sørlandet sykehus
    • Contact: Unn Ljøstad; Phone Number: +4741208824; Email: unn.ljostad@sshf.no
    • Principal Investigator: Unn Ljøstad
  • Lillehammer, Norway
    • Not yet recruiting
    • Sykehuset Innlandet HF
    • Contact: Grethe Kleveland; Phone Number: +4797157819; Email: Grethe.Kleveland@sykehuset-innlandet.no
    • Principal Investigator: Grethe Kleveland
  • Lørenskog, Norway
    • Not yet recruiting
    • Akershus University Hospital
    • Contact: Ola Nakken; Phone Number: +4797659796; Email: ola.nakken@gmail.com
    • Principal Investigator: Ola Nakken
  • Molde, Norway
    • Not yet recruiting
    • Helse Møre og Romsdal
    • Contact: Åse Morsund; Phone Number: +4747756360; Email: Ase.Hagen.Morsund@helse-mr.no
    • Principal Investigator: Åse Morsund
  • Namsos, Norway
    • Not yet recruiting
    • Helse Nord-Trøndelag HF
    • Contact: Kristina Devik; Phone Number: +4798833255; Email: Kristina.Devik@helse-nordtrondelag.no
    • Principal Investigator: Kristina Devik
  • Oslo, Norway
    • Not yet recruiting
    • Oslo Univerity Hospital
    • Contact: Angelina Maniaol; Phone Number: +4797674106; Email: angman@ous-hf.no
    • Principal Investigator: Angelina Maniaol
  • Sarpsborg, Norway
    • Not yet recruiting
    • Sykehuset Østfold HF
    • Contact: Erika Hallerstig; Phone Number: +4798455652; Email: erika.carina.hallerstig@so-hf.no
    • Principal Investigator: Erika Hallerstig
  • Skien, Norway
    • Not yet recruiting
    • Sykehuset i Telemark HF
    • Contact: Anne Berit Jøntvedt; Phone Number: +4747262912; Email: joan@sthf.no
    • Principal Investigator: Anne Berit Jøntvedt
  • Stavanger, Norway
    • Not yet recruiting
    • Stavanger University Hospital
    • Contact: Katrin Ruth Schlüter; Phone Number: +4745236149; Email: katrin.schluter@sus.no
    • Principal Investigator: Katrin Ruth Schlüter
  • Tromsø, Norway
    • Not yet recruiting
    • Universitetssykehuset Nord-Norge
    • Contact: Margitta Kampmann
    • Principal Investigator: Margitta Kampmann
  • Trondheim, Norway
    • Not yet recruiting
    • St. Olavs Hospital HF
    • Contact: Helene Ballo Kvernmo; Phone Number: +4791167718; Email: Helene.Ballo.Kvernmo@stolav.no
    • Principal Investigator: Helene Ballo Kvernmo
  • Tønsberg, Norway
    • Not yet recruiting
    • Sykehuset i Vestfold HF
    • Contact: Nicolai Johan Brun; Phone Number: +4793243780; Email: nicolai.j.brun@siv.no
    • Principal Investigator: Nicolai Johan Brun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, fronto temporal dementia (FTD) or other neurodegenerative disorder interfering 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: NO-ALS Extension Study High Dose EH301	Dietary supplement: EH301 (Nicotinamide Riboside/Pterostilbene); 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.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as how many are alive or not requiring continuous respiratory ventilation life support.	Determined after 12 months of follow-up.

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: Elysium Health
• Investigators: Principal Investigator: Ole-Bjørn Tysnes, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: October 15, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 266376

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No