Parkinson’s disease psychosis Mental and Behavioural Disorders Parkinson disease
Conditions
Interventions
The first phase is a multi-centre, open-label, safety, tolerability and dose-finding study of cannabidiol (CBD). CBD will be given orally, once per day for 6 weeks in different doses as per dosing pro
Sponsors
King’s College London and South London & Maudsley NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
40 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Satisfy established diagnostic criteria (NINDS-NIMH criteria for the diagnosis of Parkinson’s disease psychosis) and UK Brian Bank criteria for idiopathic Parkinson’s disease 2. Age 40 years or older 3. For psychotic symptoms, they should have developed after the PD diagnosis and should have been present for at least 1 month, occurring at least weekly over the month before screening and should have a combined score of at least 6 or an individual score of at least 4 on the neuropsychiatric inventory (NPI) A (delusions) and/or B (hallucinations) subscale in the month before screening 4. Parkinson’s disease dementia would not be an exclusion criterion 5. Participants with score greater than 18 on the Montreal Cognitive Assessment scale 6. Treatment as usual will include patients on quetiapine and/ or cholinesterase inhibitors (rivastigmine/ donepezil) as well as standard antiparkinsonian treatments with dosage stable for at least 1 month 7. At least 6 months post stereotaxic surgery (deep brain stimulation) and stimulator settings stable for at least 1 month prior to baseline and must remain stable during the trial 8. Ability to participate in study evaluation and ingest oral medication 9. Reliable informant/caregiver 10. Written informed consent to participate
Exclusion criteria
Exclusion criteria: 1. Insufficient understanding of trial 2. History of significant psychotic disorders prior to or concomitantly with the diagnosis of Parkinson’s disease including, but not limited to, schizophrenia or bipolar disorder 3. Psychotic symptoms secondary to other toxic or metabolic disorders 4. Psychosis onset after ablative stereotaxic surgery 5. Diagnosis of dementia made concurrent with or prior to a PD diagnosis 6. Patients on clozapine due to the requirement of special safety monitoring required for clozapine, which will unblind the safety 7. Patients taking part in another intervention trial concurrently. However, those withdrawn from another study or who have recently completed another intervention study will be eligible for inclusion if they satisfy study inclusion/ exclusion criteria. For pharmacological intervention, they will be eligible only after a sufficient period of washout (~ 5 times half-life of other study drug) 8. Participant no longer able to report symptoms as a result of cognitive impairment 9. Presence of depressive symptoms would not be an exclusion criterion. However, we would exclude those participants who may have severe depression 10. Participants who answer "yes" on the C-SSRS Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred within the last 6 months, OR Participants who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behaviour) and whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal Behavior items occurred within the last 2 years, OR Participants who, in the opinion of the investigator, present a serious risk of suicide 11. Any medical or psychological condition or social circumstances which may impair their ability to participate reliably in the study, or who may increase the risk to themselves or others by participating in the study 12. Significant ocular pathology 13. Concomitant medication that has a clinically relevant interaction with the CYP2C19 or CYP3A classes of liver enzymes will not be permitted from two weeks before inclusion until the end of the study. Examples of co-medication that will be not allowed will include CYP3A4 inhibitors (such as itraconazole, ketoconazole, posaconazole, fluconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, telaprevir, boceprevir, imatinib, ticagrelor, voriconazole), CYP3A4 inducers (such as carbamazepine, efavirenz, nevirapin, etravirin) and CYP2C19 inhibitors (such as moclobemine, fluvoxamine, chloramphenicol, fluoxetine) 14. Female patients who are pregnant or lactating 15. Female patients of childbearing potential who are not willing to use a highly effective method of contraception for the duration of the trial to prevent pregnancy, or abstain from heterosexual activity *Females of childbearing potential are females who have experienced menarche and are not surgically sterilised (e.g. by hysterectomy, bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). ** Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. combined (oestrogen and progestogen containing) hormonal c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part I: 1. Maximum tolerated dose of CBD determined by the number of dose-limiting toxicities occurring throughout the study 2. Safety and tolerability of CBD assessed by evaluating treatment-emergent adverse events, UKU side effect rating scale for psychotropic drugs, physical examination (vital signs, ECG and neurological assessment) and laboratory tests at every visit Part II: Safety and tolerability of CBD assessed by evaluating treatment-emergent adverse events, UKU side effect rating scale for psychotropic drugs, physical examination (vital signs, ECG and neurological assessment) and laboratory tests at every visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Part I: 1. Drug-drug interaction with any of the safe and tolerated doses of CBD, assessed by measuring the change in CBD and quetiapine and its metabolite and/ or donepezil levels in the blood at baseline (pre-treatment) and weeks 2 and 6 2. Evidence of neuropsychiatric drug activity (pharmacodynamic signal) measured using Parkinson’s disease-adapted scale for assessment of positive symptoms of psychosis (SAPS-PD) and Neuropsychiatric Inventory (NPI) at baseline (pre-treatment) and week 6 3. Non-motor symptoms of Parkinson’s Disease measured using the non-motor assessment scale for PD (NMSS) at baseline (pre-treatment) and week 6 4. Quality of life measured using the Parkinson’s disease questionnaire-39 (PDQ-39) at baseline (pre-treatment) and week 6 5. Sleep measured using SCOPA-Sleep at baseline (pre-treatment) and week 6 6. Cognition measured using SCOPA-COG and MoCA at baseline (pre-treatment) and week 6 7. Global improvement/change measured using the Clinical Global Impression of Change at baseline (pre-treatment) and week 6 8. Caregiver burden measured using the Zarit Burden Interview at baseline (pre-treatment) and week 6 9. Motor symptoms of Parkinson’s disease measured using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) at baseline (pre-treatment) and week 6. Part II: 1. Drug-drug interaction with any of the safe and tolerated doses of CBD, assessed by measuring the change in CBD and quetiapine and its metabolite and/or donepezil levels in the blood at baseline (pre-treatment) and weeks 2, 6 and 12 2. Evidence of neuropsychiatric drug activity (pharmacodynamic signal) measured using Parkinson’s disease-adapted scale for assessment of positive symptoms of psychosis (SAPS-PD) and Neuropsychiatric Inventory (NPI) at baseline (pre-treatment) and week 12 3. Non-motor symptoms of Parkinson’s Disease measured using the non-motor assessment scale for PD (NMSS) at baseline (pre-treatment) and week 12 4. Quality of life measured using the Parkinson’s dis | — |
Countries
England, Scotland, United Kingdom, Wales
Contacts
Public ContactKatie McGoohan
Outcome results
None listed