MEDICAL CANNABIS FOR NEURODEGENERATIVE DISEASES: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II CLINICAL TRIAL (NEUROBIS)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 186
- Locations
- 2
- Primary Endpoint
- To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving Quality of Life, assessed with the Short Form 36 Health Survey (SF-36), compared to placebo.
Study Overview
Brief Summary
It will be determined whether the use of a balanced THC/CBD extract (cannabis extract Avextra 10/10 oral solution) is safe and suitable for contributing to a significant improvement in quality of life (QoL) in patients with a neurodegenerative disease (Alzheimer’s disease (AD), Parkinson’s disease (PD), or Amyotrophic Lateral Sclerosis (ALS).
To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving Quality of Life, assessed with the Short Form 36 Health Survey (SF-36), compared to placebo.
To assess for the total study population the safety and tolerability, incidence of treatment-emergent adverse events (TAEDs) and discontinuation rate of cannabis extract Avextra 10/10 compared to placebo.
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •For all patients: ability to give written informed consent personally or, as an alternative, via a legally authorized representative. Patients >55years aged.
- •Alzheimer's Disease (AD): age diagnosis of AD based on the DSM-5 criteria for Major Neurocognitive Disorder due to AD; MMSE ≤ 24; presence of clinically significant agitation (Neuropsychiatric Inventory-agitation subscale ≥3). If treated with cognitive-enhancing medications (cholinesterase inhibitors (ChEIs) and/or memantine), the dosage must be stable for at least 3 months. If the ChEI and/or memantine have been discontinued, they may enroll after one month.
- •Amyotrophic Lateral Sclerosis (ALS): diagnosis of definite or probable according to El Escorial Criteria, documented progression of the disease in the last three months as measured by the ALSFRS-R scale (decrease of at least one point); age FVC ≥60% of predicted; treatment with riluzole 50 mg twice/day for at least one month before the screening visit.
- •Parkinson's Disease (PD): diagnosis of idiopathic Parkinson’s disease; modified Hoehn and Yahr stage 1 to 4; able to walk > 10 mt without aids or assistance; in treatment with L-Dopa with a stable dosage for at least 30 days.
Exclusion Criteria
- •Current significant cardiovascular disease (e.g., uncontrolled hypertension, clinically significant ischemic heart disease, clinically significant arrhythmia or severe heart failure).
- •Clinically significant delusions and/or hallucinations.
- •Pregnancy and breastfeeding.
- •Inability to provide inform consent.
- •Chronic infections (HBV, HCV, HIV, tuberculosis)
- •Renal (serum creatinine > 2 mg/dl or creatinine clearance < 30 mL/min according to Cockcroft-Gault formula) and hepatic (ALT, AST, GGT, alkaline phosphatase > 2.5 ULN) failure.
- •Orthostatic hypotension.
- •Presence or history of other psychiatric disorders or neurological conditions (e.g., psychotic disorders, schizophrenia, epilepsy, attempted suicide, depression)
- •Alcohol and drug abuse.
- •Current use of cannabinoids or previous or current abuse or dependence on marijuana.
- •Contraindications to cannabidiol (history of hypersensitivity to any cannabinoid).
- •Change in psychotropic medications less than 1 month prior to study inclusion (e.g., concomitant antidepressants).
Outcomes
Primary Outcomes
To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving Quality of Life, assessed with the Short Form 36 Health Survey (SF-36), compared to placebo.
To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving Quality of Life, assessed with the Short Form 36 Health Survey (SF-36), compared to placebo.
To assess for the total study population the safety and tolerability, incidence of treatment-emergent adverse events (TAEDs) and discontinuation rate of cannabis extract Avextra 10/10 compared to placebo.
To assess for the total study population the safety and tolerability, incidence of treatment-emergent adverse events (TAEDs) and discontinuation rate of cannabis extract Avextra 10/10 compared to placebo.
Secondary Outcomes
- To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving caregiver distress as assessed by a structured interview by an expert neuropsychologist using the Zarit Burden Interview (22-items) and the Caregiving Distress Scale.
- To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving a patient-reported outcome measure evaluated through the Patient Global Impression of Change (PGIC) compared to placebo.
- To demonstrate in the subpopulation of patients with Alzheimer’s disease (AD) superiority with regards to improvements on specific clinical disease marker functional disability using the standardized Mini Mental Status Examination (MMSE) to evaluate the cognitive functions and the Neuropsychiatric Inventory-agitation subscale for agitation in AD.
- To demonstrate in the subpopulation of patients with Amyotrophic Lateral Sclerosis superiority with regards to improvements on specific clinical disease marker functional disability using the ALS functional rating scale - revised (ALSFRS-R) score for functional status in ALS.
- To demonstrate in the subpopulation of patients with Parkinson’s disease superiority with regards to improvements on specific clinical disease marker functional disability using the unified Parkinson's disease rating scale (UPDRS) for monitoring the longitudinal course of PD.
Investigators
Letizia Mazzini
Scientific
Azienda Ospedaliero-Universitaria Maggiore Della Carita