None listed
Conditions
Brief summary
The aim of this study is to understand whether or not treatment with Probucol supports cognitive function in participants with MCI/mild-dementia due to AD. The trial is specifically designed to provide evidence that treatment with Probucol may slow the decline of cognitive ability and functional state. The presence of cognitive impairment will be assessed using neuro-cognitive assessments. Participants will be randomly assigned to one of two groups, group 1 (placebo) or group 2 (treatment). This is a double-blind trial meaning the participant and study doctor will not be aware which group the participant has been randomised to. The study will be 104 weeks in duration (2 years). Participants will be required to take one tablet a day (with food) for the first three weeks, and then two tablets a day (morning and night, with food) for the remainder of the trial. During the screening/pre-baseline phase participants will be asked about their medical history, complete a physical and neurological examination, an Electrocardiogram (ECG), and a blood test. Participants will also complete Neuro-cognitive assessments (memory and thinking tasks), as well as a Magnetic Resonance Imaging (MRI) scan and/or a Positron emission tomography (PET) scan. During the treatment phase, participants will be required to visit the study doctor on 10 separate occasions (once a week for the first 3 weeks, and then at approximately 3 monthly intervals). Each visit will involve a health and safety assessment. Neuro-cognitive assessments will also be conducted at week 26 (6 months), 52 (12 months), and 78 (18 months). A blood sample will also be taken at each visit. At completion of the treatment phase (week 104), participants will recomplete the Neuro-cognitive assessments, MRI and/or PET scan, and provide a final blood sample. During the course of the trial, participants will be required to nominate a 'study partner' (spouse/partner/carer). The study partner will need to attend at least one screening visit. In addition, study partners should make themselves available by phone or preferably in person, to provide information to the study as required. Participants will need to identify a study partner to be eligible to take part in this study.
Interventions
The PIA-Study is a randomised controlled research trial examining whether intervention with Probucol supports cognitive function in AD. Participants are randomly assigned to one of two groups, group 1 (placebo) or group 2 (treatment).
After consenting to participate in the study, screening procedures will occur between Days -56 and -1. All subjects must have measurable mild or moderate Alzheimer’s disease, and accordingly screening procedures will include:
• A positive amyloid biomarker (PET sca
The PIA-Study is a randomised controlled research trial examining whether intervention with Probucol supports cognitive function in AD. Participants are randomly assigned to one of two groups, group 1 (placebo) or group 2 (treatment). After consenting to participate in the study, screening procedures will occur between Days -56 and -1. All subjects must have measurable mild or moderate Alzheimer’s disease, and accordingly screening procedures will include: • A positive amyloid biomarker (PET scan) indicative of AD pathology, • Mini-mental-state examination (MMSE) score of 20 or greater, • Free and cued selective reminding test (FCSRT) cueing index score of less than or equal to 0.79, OR a free recall of less than or equal to 17. • Clinical Dementia Rating (CDR) global score of 0.5 or 1.0. Treatment: Chemical name: 4,4’-[Propan-2,2-diylbis(sulfandiyl)]bis[2,6-bis(1,1- dimethylethyl) phenol] The proposed dose of Probucol for this protocol adopts contemporary usage published in contemporary clinical trials at 250 mg twice a day. Probucol will be supplied in a commercially available form known as Lorelco. Study medication will commence (day 1, week 1) with a single dose escalation design with all participants receiving initially for two-weeks 1 X placebo per day. Unused medication is to be returned at every visit to monitor drug compliance. Thereafter, participants will be randomised into the two groups. Arm 1 (treatment) Subjects will be dosed as: • Week 3: 1 x 250 mg Lorelco™ (or matching placebo) taken in the morning, with food. • Week 4 – 104: 1 x 250 mg Lorelco™ (or matching placebo) taken in the morning, with food. 1 x 250 mg probucol (or matching placebo) taken in the evening, with food. Study medication will be dispensed as a 2-week supply for 1 interval (weeks 1 & 2); a 2-week supply for weeks 3 & 4; followed by 2 X 10-week supplies and 6 X 13 week supply dispensed at each visit. Unused medication is to be returned at every visit to monitor drug compliance.
Sponsors
Curtin University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
18 years of age or older, A positive amyloid biomarker (PET scan) indicative of AD pathology, Mini-mental-state examination (MMSE) score of 20 or greater, Free and cued selective reminding test (FCSRT) cueing index score of less than or equal to 0.79, OR a free recall of less than or equal to 17. Clinical Dementia Rating (CDR) global score of 0.5 or 1.0. A study partner (partner/spouse/carer) consents to the minimum requirements: Study partner will attend at least one screening visit Study partner will be available via phone or in person to provide information to the study as required
Exclusion criteria
A patient who meets any of the following exclusion criteria will not be eligible for inclusion in the study: 1. Recorded number of falls in previous 12 months and during trial. Participants who report multiple falls with potential loss of consciousness will be excluded 2. History of QTc-induced prolongation and willingness to limit use of over-the- counter, or prescription medicines (e.g. anti-histamines) known to prolong QTc interval. Corrected QT interval using Bazett's formula (QTcB) interval > 490 msec for males, or 500 msec for females, as detected by ECG and confirmed by physician. Participants who have a history of QTc-induced prolongation and are unwilling to limit use of medication will be excluded. 3. Evidence of abnormal cardiac function as defined by any of the following: a. Myocardial infarction within 6 months of Cycle 1, Day 1 b. Symptomatic congestive heart failure (New York Heart Association > Class II) c. Unstable angina d. Unstable atrial fibrillation including paroxysmal atrial fibrillation. Medicated, stable atrial fibrillation will be assessed by the study doctor on a case-by-case basis. e. Frequent multifocal ventricular arrhythmia 4. Unable to swallow oral medications. 5. Gastrointestinal conditions that, in the opinion of the Investigator, could affect the absorption of study drug. 6. Use of any prescription or non-prescription (including herbal) medications, or consumption of foods known to be strong QT prolongation within 7 days prior to the first administration of Lorelco™ and for the duration of the study . These include (but are not limited to): a. Medications b. With significant central anticholinergic effects, c. Sedatives, d. Antiparkinsonian medications that cannot be stopped prior to study entry, e. Any investigational treatment for AD 7. ‘Current diagnosis of cancer (within 3 years) and/or undergoing chemotherapy, with exception to cancers of the skin such as basal or squamous cell carcinoma in situ of the skin. 8. Significant head injury within 5 years 9. Electrolyte imbalance (e.g. on high steroids, pituitary tumours, and Addison disease) 10. Hypokalaemia, hypomagnesaemia and hypocalcaemia 11. They have other neurologic or psychiatric diagnosis that in the opinion of the investigator could interfere with cognitive function, 12. Major surgery is planned during the conduct of the trial, or a clinical event has occurred in the six months preceding study inclusion that may compromise ability to participate for the duration of the study, 13. Evidence of stroke where the clinical effects are clearly temporally related to the onset of cognitive impairment. 14. Current diagnosis with a psychiatric disorder, or taking psychotropic medications, 15. Other excluded medications will be those that are; • Specifically contraindicated with Probucol, based on historic clinical indications for the treatment of cardiovascular disease. Stable use (for at least 3 months) of cholinesterase inhibitors and memantine will be allowed. • Patients on high dose loop-diuretics or thiazide diuretic medications, will be excluded if taking maximum dose of furosemide or Bendroflumethiazide 16. Self-reported human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B (HBsAg) or hepatitis C virus (HCV). 17. Any inflammatory or chronic pain condition that necessitates regular use of opiates/opioids, 18. Major surgery within 28 days of Cycle 1, Day 1, or minor surgical procedures within 7 days of Cycle 1, Day 1. Exception: no waiting period applies following port-a-cath placement for venous access. 19. For women of childbearing potential, a positive pregnancy test at screening, or on Day 1, prior to dose administration. 20. Pregnant or breast-feeding (or planning to breastfeed) while on study through 15 days after the last dose of study drug. 21. Hypersensitivity or other clinically significant reaction to the study drug or its inactive ingredients. 22. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the patient’s participation in the clinical study or evaluation of the clinical study results. 23. Any other condition or prior therapy that in the opinion of the Investigator would make the patient unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements
Outcome results
None listed