NF-κB Inhibition in Amyotrophic Lateral Sclerosis (NIALS)
Primary Purpose
ALS
Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Withania somnifera
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for ALS focused on measuring Withania somnifera, Ashwagandha, Nuclear Factor Kappa Beta Inhibition, Amyotrophic Lateral Sclerosis
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:
- Substance abuse within the past year
- Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease
- Acquired Immunodeficiency Syndrome (AIDS) or AIDS-related complex
- 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
Sites / Locations
- Sunnybrook Health Sciences CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
High dosage Withania somnifera
Medium dosage Withania somnifera
Placebo
Arm Description
544mg oral twice a day
272mg oral twice a day
Matched capsules twice a day
Outcomes
Primary Outcome Measures
Incidence of adverse events (safety)
Incidence of adverse events
Secondary Outcome Measures
Change in SICI values
Short-interval intracortical inhibition (SICI) measured by transcranial magnetic stimulation (TMS).
Change in RMT values
Resting motor threshold (RMT) measured by transcranial magnetic stimulation (TMS).
Change in recovery cycle
This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).
Change in strength duration time constant
This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).
Full Information
NCT ID
NCT05031351
First Posted
August 5, 2021
Last Updated
June 1, 2022
Sponsor
Sunnybrook Health Sciences Centre
1. Study Identification
Unique Protocol Identification Number
NCT05031351
Brief Title
NF-κB Inhibition in Amyotrophic Lateral Sclerosis
Acronym
NIALS
Official Title
Nuclear Factor Kappa Beta Inhibition in Patients With Amyotrophic Lateral Sclerosis: A Phase II Randomized Placebo Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2021 (Actual)
Primary Completion Date
July 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ALS
Keywords
Withania somnifera, Ashwagandha, Nuclear Factor Kappa Beta Inhibition, Amyotrophic Lateral Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High dosage Withania somnifera
Arm Type
Experimental
Arm Description
544mg oral twice a day
Arm Title
Medium dosage Withania somnifera
Arm Type
Experimental
Arm Description
272mg oral twice a day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matched capsules twice a day
Intervention Type
Drug
Intervention Name(s)
Withania somnifera
Intervention Description
Nuclear Factor Kappa Beta Inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator
Primary Outcome Measure Information:
Title
Incidence of adverse events (safety)
Description
Incidence of adverse events
Time Frame
From Baseline visit until end of study visit (Week 9)
Secondary Outcome Measure Information:
Title
Change in SICI values
Description
Short-interval intracortical inhibition (SICI) measured by transcranial magnetic stimulation (TMS).
Time Frame
Baseline to 8 weeks
Title
Change in RMT values
Description
Resting motor threshold (RMT) measured by transcranial magnetic stimulation (TMS).
Time Frame
Baseline to 8 weeks
Title
Change in recovery cycle
Description
This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).
Time Frame
Baseline to 8 weeks
Title
Change in strength duration time constant
Description
This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).
Time Frame
Baseline to 8 weeks
Other Pre-specified Outcome Measures:
Title
Incident cases of ALSFRS-R score changes of 4 or more points
Description
Any incident case of ≥ 4-point increase in the ALS Functional Rating Scale-Revised (ALSFRS-R) scores or significant clinical improvement at week 8 will be reported. Changes in pro-inflammatory tests (CRP and IL-6) from baseline to Week 8 will be assessed.
Time Frame
Baseline to 9 weeks
Title
Change in serum IL-6 levels
Description
Serum IL-6 levels will serve as an indirect marker of NF-kB inhibition and target engagement.
Time Frame
Baseline to 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
Substance abuse within the past year
Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease
Acquired Immunodeficiency Syndrome (AIDS) or AIDS-related complex
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jake Wimmer
Phone
416-480-6100
Ext
87561
Email
jake.wimmer@sri.utoronto.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Shirley Pham
Phone
+1 (416)480-6860
Email
shirley.pham@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Agessandro Abrahao, MD, MSc
Organizational Affiliation
Sunnybrook Research Institute, University of Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lorne Zinman, MD, MSc
Organizational Affiliation
Sunnybrook Research Institute, University of Toronto
Official's Role
Study Director
Facility Information:
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lorne Zinman
Email
Lorne.Zinman@sunnybrook.ca
First Name & Middle Initial & Last Name & Degree
Agessandro Abrahao
Email
agessandro.abrahao@sunnybrook.ca
12. IPD Sharing Statement
Learn more about this trial
NF-κB Inhibition in Amyotrophic Lateral Sclerosis
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