Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000307404
Ethics application status
Approved
Date submitted
17/02/2025
Date registered
16/04/2025
Date last updated
16/04/2025
Date data sharing statement initially provided
16/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Single dose study to determine the effect of guanfacine on cognition and brain activity in Parkinson’s disease
Scientific title
Single dose study to determine the effect of guanfacine on cognition and brain activity in Parkinson’s disease
Secondary ID [1] 313851 0
Nil known
Universal Trial Number (UTN)
Trial acronym
alphaPUG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 336546 0
Condition category
Condition code
Neurological 333061 333061 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 330465 0
Treatment: Drugs
Comparator / control treatment
A single dose of placebo (microcrystalline cellulose) administered as an oral gelatin capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 340643 0
Accuracy in neutral condition
Timepoint [1] 340643 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Primary outcome [2] 340647 0
Accuracy in maintenance condition
Timepoint [2] 340647 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Primary outcome [3] 340648 0
Change in outcome measure of stop signal reaction time
Timepoint [3] 340648 0
5 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [1] 446048 0
Apathy
Timepoint [1] 446048 0
Baseline, 4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [2] 446057 0
[Primary Outcome] Accuracy in manipulation condition
Timepoint [2] 446057 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [3] 444697 0
Locus coeruleus integrity
Timepoint [3] 444697 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [4] 446044 0
[Primary outcome] Accuracy in interference condition
Timepoint [4] 446044 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [5] 444699 0
Anxiety
Timepoint [5] 444699 0
Baseline, 4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [6] 446059 0
[Primary Outcome] Reaction time in manipulation condition
Timepoint [6] 446059 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [7] 444695 0
Change in plasma guanfacine levels
Timepoint [7] 444695 0
3.5 hours post dose (active treatment) and 3.5 hours post dose (placebo)
Secondary outcome [8] 444698 0
Change in brain functional connectivity at rest
Timepoint [8] 444698 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [9] 446047 0
Depression
Timepoint [9] 446047 0
Baseline, 4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [10] 444696 0
Mood
Timepoint [10] 444696 0
Baseline, 3.5 hours post dose and 6 hours post dose in both active treatment and placebo conditions
Secondary outcome [11] 446045 0
[Primary outcome] Brain network activation
Timepoint [11] 446045 0
4 hours post dose (active treatment) and 4 hours post-dose (placebo)
Secondary outcome [12] 446046 0
Arousal
Timepoint [12] 446046 0
Baseline, 3.5 hours post dose and 6 hours post dose in both active treatment and placebo conditions
Secondary outcome [13] 446055 0
[Primary outcome] Reaction time in neutral condition
Timepoint [13] 446055 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [14] 446049 0
Apathy
Timepoint [14] 446049 0
Baseline, 4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [15] 446056 0
[Primary outcome] Reaction time in interference condition
Timepoint [15] 446056 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [16] 446060 0
[Primary outcome] Brain network activation
Timepoint [16] 446060 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [17] 446050 0
Sleep behavour
Timepoint [17] 446050 0
Baseline, 4 hours post dose (active treatment) and 4 hours post dose (placebo)
Secondary outcome [18] 446058 0
[Primary Outcome] Reaction time in maintenance condition
Timepoint [18] 446058 0
4 hours post dose (active treatment) and 4 hours post dose (placebo)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/06/2025
Actual
Date of last participant enrolment
Anticipated
30/10/2026
Actual
Date of last data collection
Anticipated
31/03/2027
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 318317 0
Government body
Name [1] 318317 0
National Health and Medical Research Council
Country [1] 318317 0
Australia
Primary sponsor type
University
Name
Macquarie University
Address
Country
Australia
Secondary sponsor category [1] 320709 0
None
Name [1] 320709 0
Address [1] 320709 0
Country [1] 320709 0
Other collaborator category [1] 283415 0
University
Name [1] 283415 0
The University of Sydney
Address [1] 283415 0
Country [1] 283415 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316952 0
Macquarie University Human Research Ethics Committee Medical Sciences
Ethics committee address [1] 316952 0
Ethics committee country [1] 316952 0
Australia
Date submitted for ethics approval [1] 316952 0
24/10/2024
Approval date [1] 316952 0
08/01/2025
Ethics approval number [1] 316952 0
17788

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139542 0
Dr Claire O'Callaghan
Address 139542 0
Brain and Mind Centre, 94 Mallett Street Camperdown NSW 2050
Country 139542 0
Australia
Phone 139542 0
+61 402 245 053
Fax 139542 0
Email 139542 0
[email protected]
Contact person for public queries
Name 139543 0
Dr Claire O'Callaghan
Address 139543 0
Brain and Mind Centre, 94 Mallett Street Camperdown NSW 2050
Country 139543 0
Australia
Phone 139543 0
+61 402 245 053
Fax 139543 0
Email 139543 0
[email protected]
Contact person for scientific queries
Name 139544 0
Dr Claire O'Callaghan
Address 139544 0
Brain and Mind Centre, 94 Mallett Street Camperdown NSW 2050
Country 139544 0
Australia
Phone 139544 0
+61 402 245 053
Fax 139544 0
Email 139544 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Sharing of data with other research sites will be subject to conditions including (i) not to be used for commercial purposes (ii) not for third-party sharing (iii) that no attempt will be made to undermine anonymity or to identify participants (iv) and that local curation will adhere to the recipients’ national standards for data curation to preserve anonymity. Researchers wishing to receive data would be required to agree to the terms and conditions before gaining access to the data.

What individual participant data might be shared?
• Anonymised neuroimaging data will be made available in the international standard of unprocessed ‘DICOM’ files and behavioural performance data files for the fMRI tasks. De-identified participant data supporting publication results will be shared for questionnaires and cognitive tasks. This data will include a minimal set of clinical and demographic information supporting publication results.

What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Data repository: Data will be hosted on the Macquarie University Research Data Repository. Data will be made available via mediated/restricted access, which limits reuse of the data for non-commercial purposes only, and only so long as attribution is given to the creator, with any reuse of the data to be licensed under identical terms.

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.