None listed
Conditions
Brief summary
This study aims to investigate the effect of a single dose of guanfacine on cognition and brain function in people with Parkinson's disease. The purpose of the study is to determine the potential effectiveness of guanfacine in treating cognitive symptoms in Parkinson's disease. This study will involve 25 participants with Parkinson's disease, who will take part in 2 study visits at least one week apart. Each participant will receive either guanfacine (active treatment) or a placebo at one visit and the opposite at the other, in a randomised order, without knowing which one they are receiving. The effects of the medication will be measured using cognitive tests, brain scans and blood tests.
Interventions
A single 2mg dose of extended-release guanfacine hydrochloride administered as an oral tablet. Adherence to the intervention will be monitored via direct observation of dosing by study staff. A wash out period of 7 days will be implemented between treatments.
Sponsors
Macquarie University
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Parkinson's disease according to the MDS Clinical Diagnostic Criteria for Parkinson’s Disease. 2. Ability to provide written informed consent in accordance with ICH-GCP and local regulations. 3. Male or female aged up to 80 years as of the date of Visit 1. 4. Stabilised on optimal symptomatic treatment for a minimum of 4 weeks prior to the screening phone call with no significant changes expected throughout the study. 5. Willing and able to undergo trial assessments (e.g., venepuncture, MRI). 6. Willing and able to take oral drug therapy according to the study protocol.
Exclusion criteria
1. Absence of dementia based on the Movement Disorders Society (MDS) criteria for Parkinson’s disease dementia and clinical impression. 2. Contraindications to MRI as per established 3T MRI safety protocols in use at Macquarie Medical Imaging. 3. Participation in a clinical trial within the past 3 months, or current use of study drug. 4. Known hypersensitivity to any of the study drugs or their constituents. 5. History of significant medical event/s within 6 months prior to the screening visit, at the discretion of the Clinical Lead (CL). 6. Use of typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to screening that in the opinion of the CL might account for parkinsonism. 7. Gastrointestinal conditions that may affect the absorption of study drug (e.g., ulcerative colitis, gastric bypass). 8. Serious neurological disorder (e.g., epilepsy) other than PD. 9. History of head trauma with loss of consciousness for more than 5 minutes within the past 6 months. 10. Prior diagnosis of cancer and evidence of continued malignancy within the past three years (with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or in situ prostate cancer with normal prostate-specific antigens post resection). 11. Any major surgical procedure within 30 days prior to the initial screening. 12. Active alcohol or substance use disorder within the past 12 months. 13. History of uncontrolled psychotic symptoms or history of a suicidal attempt/s within the prior 6 months. 14. Any condition or laboratory test result, which in the CL’s judgment might result in an increased risk to the participant or would affect their participation in the study. 15. Participation in any trial of a device [including, but not limited to Transcranial magnetic stimulation (TMS)], NIR and red light therapy (L equal to 600–1070 nm), investigational medicinal product, supplement, surgical treatment, cognitive/behavioural therapy, physiotherapy, health food supplements or active exercise study within 30 days prior to the screening phone call. 16. Current Impulse Control Disorder (ICD) as assessed via formal brief screen (i.e., positive response on the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease; QUIP-Current-Short) and at the discretion of the CL. 17. Abnormal ECG results, which in the opinion of the CL would preclude participation in the study. 18. Labile blood pressure or new antihypertensive medication started within 3 weeks. 19. Severe coronary insufficiency or myocardial infarction in the previous 6 months. 20. History of unexplained syncope within the preceding 12 months. 21. Cardiac conduction block. 22. Severe hepatic impairment (ALT greater than 120, ALP greater than 390 and total bilirubin greater than 60). 23. Severe renal impairment (eGFR less than 40) 24. Treatment with medications known to potentiate guanfacine’s hypotensive effects or cause arrhythmia (antipsychotics including aripiprazole, sultopride, chlorpromazine, thioridazine, amisulpiride, sulpiride, haloperidol), moxifloxacin, baclofen, verapamil, quinidine, hydroquinidine, dispyramide, amiodarone, dofetilide, ibutilide, sotalol, pimazide, bepridil, casipride, diphemanil, erythromycin, halofantrine, pentamidine, sparfloxacin, vincamine, alfuzosin, prazosin, terazosin, tamsulosin and amifostine. Treatment with contradictions to guanfacine: As per the criteria in a current phase III trial of extended-release guanfacine in participants with mild to moderate Alzheimer’s disease supported by Imperial College Healthcare NHS Trust and the NIHR Biomedical Research Centre at Imperial College London UK (NCT03116126 – yet to report), based on the European Medicines Agency (EMA) approved Summary of Product Characteristics (SmPC). The following drugs should not be commenced during the trial: Ketoconazole, rifampicin, sodium valproate, beta blockers, non- dihydropyridine calcium channel blockers, cholinesterase inhibitors and sphingosine-1 phosphate receptor modulators. The following drugs, which can increase the QT interval, should not be commenced during the trial: Class IA antiarrhythmics (e.g. quinidine, procainamide, disopyramide), class III antiarrhythmics (e.g. amiodarone, sotalol, ibutilide, dronedarone), class 1C antiarrhythmics (e.g. flecainide, propafenone), antipsychotics (e.g. chlorpromazine, pimozide, haloperidol, droperidol, ziprasidone), antidepressants (e.g. fluoxetine, citalopram, venlafaxine, tricyclic/ tetracyclic antidepressants, e.g. amitriptyline, imipramine, maprotiline), opioids (e.g. methadone), macrolide antibiotics and analogues (e.g. erythromycin, clarithromycin, telithromycin, tacrolimus), quinolone antibiotics (e.g. moxifloxacin, levofloxacin, ciprofloxacin), antimalarials (e.g. quinine, chloroquine), azole antifungals (e.g. ketoconazole, fluconazole, voriconazole), domperidone, 5-HT3 receptor antagonists (e.g. dolasetron, ondansetron), tyrosine kinase inhibitors (e.g. sunitinib, nilotinib, lapatinib), histone deacetylase inhibitors (e.g. vorinostat) and beta-2 adrenoceptor agonists (e.g. salmeterol, formoterol). To minimise the possible sedative side effects of guanfacine, the following central nervous system (CNS) depressants should not be commenced during the trial: Sedatives, hypnotics, benzodiazepines, barbiturates, antipsychotics, and oral methylphenidate. 25. Weight under 45 kg (in order to ensure that an excessive dose per body weight is not used in the study). 26. Pregnancy (pre-menopausal women will only be entered into the study if they are surgically sterile or using effective birth control methods: these are abstinence for the period of the study, intrauterine contraception/device, male sexual partners with vasectomy).
Outcome results
None listed