Table V-.
Clinical trials in progress to study the effect of RAS modulators on cognition
| 1. Telmisartan vs. Perindopril in Hypertensive Mild-Moderate Alzheimer’s Disease Patients (SARTAN-AD) [80]. | |
|---|---|
| ClinicalTrials.gov Identifier: | NCT02085265 |
| Condition or disease | Alzheimer’s Disease and Hypertension |
| Study design | Randomized, Open Label Clinical Trial with Parallel drug Assignment |
| Estimated Enrollment | 240 participants |
| Intervention/treatment | - Telmisartan 40 mg or 80 mg/day (depending on age and tolerability) - Perindopril 2 mg, 4 mg or 8 mg/day (depending on renal function and tolerability) |
| Phase | Phase II |
| Study Start Date | March 2014 |
| Estimated Study Completion Date | March 2021 |
| Primary Outcome Measures | BP, Ventricular enlargement , Safety, Adverse events |
| Secondary Outcome Measures | Change in hippocampal volume, volume of grey and white matter, measures of cognitive function |
| Eligibility Criteria | Age ≥ 50 Years |
| Inclusion criteria | Probable or possible AD dementia Established diagnosis of hypertension |
| Exclusion criteria | Intolerance or contraindications to study medications FAD form of Alzheimer’s disease |
| 2. Health Evaluation in African Americans Using RAS Therapy (HEART) [81]. | |
|---|---|
| ClinicalTrials.gov Identifier: | NCT02471833 |
| Condition or disease | Alzheimer’s Disease |
| Study design | Randomized Double blinded, Interventional Clinical Trial |
| Estimated Enrollment : | 66 participants |
| Primary Purpose: | Prevention |
| Intervention/Treatment | Telmisartan 20mg or Telmisartan 40mg or Placebo each given orally once a day for 8 months |
| Phase | Phase I |
| Study Start Date | April 2015 |
| Estimated Completion Date | June 30, 2020 |
| Primary Outcome Measures | Change in concentration of CSF angiotensin metabolites [ From baseline to 8 months] |
| Secondary Outcome Measures | Changes in plasma RAS components (Renin, ACE, aldosterone) Change in CSF T-tau, P-tau Cognitive function (MMSE, WAIS, MoCA, Set-shifting Test, Flanker Inhibitory Control and Attention Test) |
| Eligibility Criteria | Age ≥30 Years |
| Inclusion criteria | African American with hypertension and Family history of AD |
| Exclusion criteria | Mean resting SBP ≥110 and ≤ 170 mmHg Current use of RAS acting medication History of stroke, Dementia, Heart failure or Diabetes Types I and II |
| 3. Candesartan’s Effects on Alzheimer’s disease And Related Biomarkers (CEDAR)[158]. | |
|---|---|
| ClinicalTrials.gov Identifier: | NCT02646982 |
| Condition or disease | Mild Cognitive Impairment |
| Study design | Randomized Quadruple Blinded (Participant, Care Provider, Investigator, Outcomes Assessor)Interventional Clinical Trial |
| Estimated Enrollment : | 72 participants |
| Intervention/Treatment | Candesartan vs matched Pacebo once daily for 12 months Candesartan will be started at 8 mg orally, once daily. The dose will be increased in 2 week increments to 16 mg and 32 mg once daily, as tolerated (SBP>110 mm Hg, DBP>40 mm Hg with no reported symptoms of hypotension). |
| Phase | Phase II / Phase III |
| Study Start Date | June 2016 |
| Estimated Completion Date | September 2021 |
| Primary Outcome Measures | Changes in the following: number of subjects with hypotension, number of hypotensive episodes, Scr and serum potassium |
|
Secondary Outcome
Measures |
Changes in CSF phospho-tau, Aβ42, cytokines Change in arterial stiffness and cerebral vasoreactivity Changes in levels of circulating EPCs Changes in cognitive function as assessed by (ADAS-cog, CDR, EXAMINER, Spatial 1-Back test) Change in WMH assessed by MRI |
| Eligibility Criteria | 60 – 85 Years (Adult, Older Adult) |
| Inclusion criteria | Mild Cognitive Impairment, with abnormal memory function and delayed recall (MoCA < 26) but general functional performance sufficiently preserved and Aβ positivity determined |
| Exclusion criteria | Intolerance to ARBs Current use of antihypertensive medication including ARBs or ACEIs Renal disease or uncontrolled congestive heart failure Inability to have MRI History of increased intracranial pressure or bleeding diathesis Women of childbearing potential (non-menopausal) |
| 4. Risk Reduction for Alzheimer’s Disease (rrAD) [157]. | |
|---|---|
| ClinicalTrials.gov Identifier: | NCT02913664 |
| Condition or disease | Cognitively Normal Older Adults |
| Study Type | Interventional (Clinical Trial), Randomized, Factorial Assignment |
| Estimated Enrollment : | 640 participants, 60 Years to 85 Years (Adult, Older Adult), all sexes. |
| Intervention/Treatment | Drug: Angiotensin II receptor blocker (ARB, losartan) and calcium channel blocker (amlodipine) |
| Phase | Phase II |
| Study Start Date | September 2016 |
| Estimated Completion Date | September 2022 |
| Primary Outcome Measures | Change in global neurocognitive function [ Time Frame: 2 Years ] |
| Secondary Outcome Measures | Assessment of domain-specific neurocognitive function Assessment of whole brain and hippocampal volume Assessment of global and regional brain perfusion Assessment of brain white matter hyperintensity (WMH) Assessment of brain white matter microstructural integrity |
| Eligibility / Inclusion criteria | Age 60–85, all races/ethnicities, and both sexes are eligible. A positive family history of dementia defined as having at least one first-degree relative with a history of AD or other type of dementia or b) having subjective cognitive decline. |
| Exclusion criteria | Clinically documented history of stroke, focal neurological signs or other major cerebrovascular diseases Diagnosis of significant neurologic diseases Uncontrolled diabetes mellitus Allergy to angiotensin receptor blockers (ARBs) |