Clinical trial NCT05031351: NF-κB Inhibition in Amyotrophic Lateral Sclerosis
Official title: Nuclear Factor Kappa Beta Inhibition in Patients With Amyotrophic Lateral Sclerosis: A Phase II Randomized Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: ALS
Keywords: Withania somnifera
Ashwagandha
Nuclear Factor Kappa Beta Inhibition
Amyotrophic Lateral Sclerosis
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2021-09-01
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase II, single centre, randomized, parallel, double blind, placebo-controlled clinical trial to determine the safety of Withania somnifera in participants with Amyotrophic Lateral Sclerosis (ALS).

Detailed description: There will be up to 75 participants randomized 1:1:1 to receive either high dosage Withania somnifera extract (1088 mg daily), medium dosage Withania somnifera extract (544 mg daily) or matching placebo. The study will consist of a Screening Period, Randomization visit, Baseline visit, and Follow-up visits. The treatment period will be 8 weeks and a final follow up call will occur at Week 9.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with laboratory supported probable, clinically possible, probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (83) (Appendix A)
* Disease duration from symptom onset no greater than 36 months at the Screening Visit
* Aged 18 years or older
* Capable of providing informed consent and complying with study procedures
* If taking riluzole, on a stable dose for at least 30 days prior to Screening Visit
* If taking edaravone, on a stable dose for at least one cycle prior to Screening Visit
* If on BiPAP, average usage of no more than 12 hours per day at time of Screening Visit
* Able to swallow a capsule at Baseline Visit
* Fluency in English or French

Exclusion Criteria:

* Exposure to any investigational agent or Withania somnifera (Ashwagandha) within 30 days prior to the Screening Visit; simultaneous participation in other observational studies is allowed upon Site Investigator approval
* Presence of any of the following clinical conditions:

  1. Substance abuse within the past year
  2. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease
  3. Acquired Immunodeficiency Syndrome (AIDS) or AIDS-related complex
  4. Unstable psychiatric illness defined as psychosis (hallucinations or delusions) or untreated major depression within 90 days prior to the Screening Visit
* Hypersensitivity or allergy to Withania somnifera
* Uncontrolled diabetes with severe associated complications (such as neuropathy)
* Untreated hypertension, active stomach ulcers, or untreated thyroid disorder
* Previously diagnosed auto-immune condition with or without neurological manifestations (e.g. multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis, etc.)
* Current or planned use of oral, intramuscular or intravenous steroid drugs (such as prednisone, prednisolone, dexamethasone, triamcinolone, methylprednisolone, oxandrolone, and others) or immunosuppressant drugs (azathioprine, mycophenolate, tacrolimus, sirolimus, cyclophosphamide, and others) for more than 7 days
* Planned consumption of alcohol, other drugs or natural health products with sedative and anxiolytics properties while taking study drugs (8 week duration)
* Current or planned use of continuous subcutaneous, intravenous or oral anticoagulant drugs
* Scheduled for surgery under general anesthetic within 14 days of Screening Visit
* Pregnancy or planned pregnancy. Women of childbearing potential must have a negative pregnancy test and be non-lactating at the Screening Visit
* Insertion of a diaphragm pacing system

Primary outcomes:
measure: Incidence of adverse events (safety)
timeFrame: From Baseline visit until end of study visit (Week 9)
Secondary outcomes:
measure: Change in SICI values
timeFrame: Baseline to 8 weeks
measure: Change in RMT values
timeFrame: Baseline to 8 weeks
measure: Change in recovery cycle
timeFrame: Baseline to 8 weeks
measure: Change in strength duration time constant
timeFrame: Baseline to 8 weeks
Other outcomes:
measure: Incident cases of ALSFRS-R score changes of 4 or more points
timeFrame: Baseline to 9 weeks
measure: Change in serum IL-6 levels
timeFrame: Baseline to 8 weeks
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Research Institute, University of Toronto
name: Agessandro Abrahao, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Research Institute, University of Toronto
name: Lorne Zinman, MD, MSc
role: STUDY_DIRECTOR
References: