Dronabinol; Cannabidiol for Neurodegenerative diseases | Amyotrophic lateral sclerosis | Alzheimer's disease | Parkinson's disease

Inclusion criteria

• {"criterion_text":"- For all patients: ability to give written informed consent personally or, as an alternative, via a legally authorized representative. Patients >55years aged.\n- 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.\n- 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.\n- 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

• {"criterion_text":"- Current significant cardiovascular disease (e.g., uncontrolled hypertension, clinically significant ischemic heart disease, clinically significant arrhythmia or severe heart failure).\n- Chronic infections (HBV, HCV, HIV, tuberculosis)\n- 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.\n- Orthostatic hypotension.\n- Presence or history of other psychiatric disorders or neurological conditions (e.g., psychotic disorders, schizophrenia, epilepsy, attempted suicide, depression)\n- Alcohol and drug abuse.\n- Current use of cannabinoids or previous or current abuse or dependence on marijuana.\n- Contraindications to cannabidiol (history of hypersensitivity to any cannabinoid).\n- Change in psychotropic medications less than 1 month prior to study inclusion (e.g., concomitant antidepressants).\n- Clinically significant delusions and/or hallucinations.\n- Pregnancy and breastfeeding.\n- Inability to provide inform consent."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Quality of Life assessed with the Short Form 36 Health Survey (SF-36) for the total study population; comparison versus placebo."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessment of safety and tolerability via incidence of treatment-emergent adverse events (TAEDs) and discontinuation rate compared to placebo."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Caregiver distress assessed by structured interview using the Zarit Burden Interview (22-items) and the Caregiving Distress Scale."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Patient-reported outcome measured by the Patient Global Impression of Change (PGIC) compared to placebo."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Cognitive function measured by MMSE and agitation by the Neuropsychiatric Inventory-agitation subscale in the AD subpopulation."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Functional status in ALS measured by ALSFRS-R score in the ALS subpopulation."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Disease severity/course in PD measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in the PD subpopulation."}

Italy

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

17-07-2024

Processing Time Days

22

Number Of Sites

2

Number Of Participants

186

Primary sponsor

Full Name

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Ministero della Salute - Direzione generale della ricerca e dell'innovazione in sanità.","duties_or_roles":"Source of monetary support","organisation_type":""}