Parkinson’s disease (PD) Nervous System Diseases
Conditions
Interventions
The EJS ACT-PD trial has three treatment arms: placebo, telmisartan and terazosin. All treatment arms are in addition to Standard of Care.
As EJS ACT-PD is a blinded trial, all participants will rece
Week 4-5: one 40 mg capsule per day
Terazosin – Week 1: one 1 mg capsule per day
Week 2: one 2 mg capsule per day
Week 3: one 3 mg capsule per day
Week 4: one 4 mg capsule per day
Week 5: one 5 mg capsule per day
If the participant tolerates the IMP dose during the titration phase, they will continue onto the treatment phase, if they are happy to do so. The treatment phase als
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis by neurologist, movement disorders specialist or appropriately experienced clinician of clinically established or clinically probable PD in the clinician’s opinion. In the presence of any diagnostic doubt, the Movement Disorder Society diagnostic criteria will be applied. 2. Diagnosed with Parkinson’s disease at age 30 years or older, no upper age limit. 3. Currently on Parkinson’s medication (levodopa-containing preparations or dopamine agonists, used either as single agents or in combination) for at least 2 months prior to the screening visit. 4. Female participants who are women of child-bearing potential (WOCP) must have confirmation of a negative pregnancy test at the screening visit. See Protocol Table 1 and Section 6.6.4 for details on pregnancy testing. 5. Female participants who are WOCP and male participants with partners who are WOCP must be taking appropriate contraceptive treatment(s). See Protocol Section 6.6.4 for details on pregnancy and Appendix 1 for details on acceptable contraception. 6. Documented informed consent. 7. Eligible for at least one of the active treatment arms (see treatment-specific exclusions). 8. Randomisation should ideally take place within 3 weeks of the screening visit but no later than 4 weeks after the screening visit. 9. If a participant is being re-randomised into the trial, additional timing of entry requirements must also be met: 9.1. For participants re-randomised after completing 36 months’ follow-up and the arm was not closed due to lack of activity, a 26-week washout period from the last dose of IMP must be completed before their screening visit. If the primary analysis indicates that the IMP was ineffective then this washout period can be reduced to 6 weeks. 9.2. For participants being re-randomised following treatment arm termination due to lack of activity, a 6-week washout period from their last dose of IMP must be completed prior to screening assessment.
Exclusion criteria
Exclusion criteria: 1. Diagnosis or suspicion of other cause for parkinsonism such as atypical parkinsonism, dystonic tremor, essential tremor, or drug-induced parkinsonism. 2. Known carriers of recessive PD gene mutations PRKN, PINK1 or DJ1 (based on previous medical tests/notes). 3. Clinical diagnosis of dementia or MoCA 14 on PHQ-9 at screening visit. 7. Current suicidal ideation within one year prior to the screening visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS). 8. Previous brain surgery or on a waiting list for brain surgery including deep brain stimulation and/or currently taking or on a waiting list for advanced therapies for Parkinson’s disease (such as any infusion therapy). 9. Monotherapy with monoamine oxidase-B inhibitor (MAO-BI). 10. Previous exposure to any of the currently recruiting IMPs within 6 months prior to the screening visit or previous intolerance of any of the IMPs. 11. Participant has any concurrent medical condition, abnormal laboratory tests, progressive neurological disorder or uncontrolled, clinically significant systemic disease that, in the opinion of the Investigator, could cause study participation to be detrimental to the participant (e.g., end-stage renal failure, severe heart failure, unstable angina, uncontrolled hypertension or uncontrolled orthostatic hypotension, severe liver disease, uncontrolled diabetes, or severe anaemia). 12. Pregnant or breastfeeding or intending to become pregnant during the study or within 70 days after the final dose of the study drug. 13. Confirmed diagnosis of cancer and is requiring active management of that cancer and/or in the view of the local team, the diagnosis and/ or its treatment may compromise their ability to remain participating in the trial for 36 months or tolerate any of the active treatments. 14. Participants with hepatobiliary disorders or abnormal liver function tests (ALT or AST >2x the upper limit of normal) at the screening visit. 15. Participants with a history of alcohol/drug abuse/dependence within the 3 years prior to the screening visit. 16. Participants with either of the following: 16.1. Sitting systolic blood pressure (SBP) less than 100 mmHg or sitting diastolic blood pressure (DBP) less than 50 mmHg, irrespective of symptoms 16.2.1. Orthostatic hypotension defined as any of the following: 16.2.2. Decrease in BP >20 mmHg systolic or >10 mmHg diastolic on supine to standing, associated with clinical symptoms 16.2.3. Decrease in BP >30 mmHg systolic and/or BP >15 mmHg diastolic on supine to standing regardless of symptoms 16.2.4. If the lowest BP on standing is less than 100 mmHg or lowest diastolic on standing is less than 50 mmHg If, in the assessing clinician’s opinion, the postural BP drop is attributable to transient/reversible factors (e.g. related to the use of antihypertensives, dehydration, elevated room temperature, postprandial state), one repeated orthostatic BP assessment is allowe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate of Parkinson’s disease progression between the active treatment and placebo arms is measured by the MDS-UPDRS Parts I and II combined with equal weighting at baseline, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165 | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinician reported measures: 1. Parkinson’s disease stage is measured using the Hoehn and Yahr Scale (H&Y) at screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165. 2. Cognitive impairment is measured using the Montreal Cognitive Assessment (MoCA) at screening, week 0, week 26, week 52, week 104, week 156 or early termination. 3. Parkinson’s disease medication use is measured by levodopa-equivalent daily dose (LEDD) at all study visits. 4. Part III of the MDS-UPDRS in the ON medication state (remote elements only) at screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165. 5. Part IV of the MDS-UPDRS in the ON medication state at screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165. 6. The severity of depression is assessed by the Patient Health Questionnaire (PHQ-9) at screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination. 7. Quality of life is assessed by the Parkinson’s Disease Questionnaire (PDQ-8) at week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination. 8. Carers' quality-of-life is assessed by the questionnaire for parkinsonism (PQoL Carers) at week 0, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination. 9. Ability to enjoy life is assessed by the ICEpop CAPability measure for Older people (ICECAP-O) at week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination. 10. Health-related quality of life is assessed by the EuroQol five-dimension scale questionnaire (EQ-5D-5L) at week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termina | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactEJS ACT-PD Trial Team at MRC CTU
Outcome results
None listed