Alzheimer's DiseasePhase 1/2HEARTNCT02471833
Health Evaluation in African Americans Using RAS Therapy
A Phase 1/2 study testing Telmisartan 20mg and Telmisartan 40mg in people with Alzheimer's Disease, run by Emory University at 1 site in United States.
Trial summary
The purpose of this study is to determine if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease prevention in African Americans, who are at high risk for Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Telmisartan 20mg and Telmisartan 40mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 15 Apr 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mean resting systolic blood pressure ≥ 110 mmHg and ≤ 170 mmHg
- Family history of Alzheimer's disease
- African American
Who cannot join
- Currently in another investigational drug study
- Potassium >5.0 meq/dL at baseline
- Creatinine >1.99 mg/dL at baseline
- History of stroke or transient ischemic attack (TIA)
- Dementia
- Current use of a RAS acting medication
Show all 10Show fewer
- Contraindication for lumbar puncture or magnetic resonance imaging
- Heart failure
- Diabetes Types I and II
- Pregnant or nursing women
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease prevention in African Americans, who are at high risk for Alzheimer's disease.
Read the detailed description
This study will assess if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease (AD) prevention in African Americans, who are at high risk for Alzheimer's disease. Blood pressure medications known as angiotensin-receptor blockers have been associated with reduced risk of Alzheimer's in Caucasians because they act on the renin-angiotensin system (RAS), a key regulator of blood pressure in the body and the brain. The drugs appear to slow the progression of the disease by affecting flow of blood and the amount of plaque in the brain, but these benefits have not been tested in African Americans. The investigator will evaluate if telmisartan is able to influence the renin-angiotensin system in the brain and produce favorable effects on brain blood flow and enzymes that cause the brain plaques in Alzheimer's disease.The investigator will assess the mechanism by which telmisartan modifies the brain renin angiotensin system, cerebrospinal fluid amyloid-β, cerebral blood flow (CBF) and inflammatory markers in hypertensive African Americans.
- Conditions
- Alzheimer's Disease
- Being tested
- Telmisartan 20mg, Telmisartan 40mg, Placebo
- Keywords
- hypertension, prevention, family history, inflammation, blood brain barrier, amyloid
- Medical subject headings
- Alzheimer Disease, Hypertension, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telmisartan 20mgDrug
Also called Micardis
Participants will be given 20 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months.
Telmisartan 40mgDrug
Also called Micardis
Participants will be given 40 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months.
PlaceboDrug
Participants will be given placebo to be taken orally once a day before bedtime, for a duration of 8 months.
| Study group | Role | What they receive |
|---|---|---|
| Telmisartan 20mg | Experimental | African American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive telmisartan 20mg once a day orally. Receives: Drug: Telmisartan 20mg |
| Telmisartan 40mg | Experimental | African American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive telmisartan 40mg once a day orally. Receives: Drug: Telmisartan 40mg |
| Placebo | Placebo comparator | African American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive a placebo to match telmisartan once a day orally. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of Angiotensin Converting Enzyme (ACE 1)
The cerebrospinal fluid renin-angiotensin system (RAS) was assessed by measuring levels of angiotensin metabolites in a 1 milliliter (mL) sample of cerebrospinal fluid (CSF). ACE 1 helps to regulate blood pressure by converting angiotensin I to angiotensin II.
Measured: Baseline, Month 8
Concentration of Angiotensin Converting Enzyme 2 (ACE 2)
The cerebrospinal fluid renin-angiotensin system (RAS) was assessed by measuring levels of angiotensin metabolites in a 1 milliliter (mL) sample of cerebrospinal fluid (CSF). ACE 2 regulates levels of circulating angiotensin II. ACE 2 increases during illness and with Alzheimer's disease.
Measured: Baseline, Month 8
Cerebrospinal Fluid Amyloid β40
Levels of amyloid β40 (Aβ40) in the cerebrospinal fluid were measured using LUMIPULSE® technology. The relationship between Aβ40 is non-linear with moderate levels showing the highest risk of future cognitive decline in some studies.
Measured: Baseline, Month 8
Levels of Cerebrospinal Fluid Amyloid β42
Levels of amyloid β42 (Aβ42) in the cerebrospinal fluid were measured using LUMIPULSE® technology. Decreases in concentrations of amyloid β42 are indicative of a decrease in cognitive function.
Measured: Baseline, Month 8
Levels of Cerebrospinal Fluid T-tau
Levels of T-tau in the cerebrospinal fluid were measured using LUMIPULSE® technology. Increases in concentrations of T-tau are indicative of a decrease in cognitive function.
Measured: Baseline, Month 8
Levels of Cerebrospinal Fluid P-tau
Levels of P-tau in the cerebrospinal fluid were measured using LUMIPULSE® technology. Increases in concentrations of P-tau are indicative of a decrease in cognitive function.
Measured: Baseline, Month 8
Secondary outcomes (14)
Interleukin-6 (IL-6) Frequency
The inflammatory marker IL-6 in CSF was examined.
Measured: Baseline, Month 8
Interleukin-7 (IL-7) Frequency
The inflammatory marker IL-7 in CSF was examined.
Measured: Baseline, Month 8
Interleukin-8 (IL-8) Frequency
The inflammatory marker IL-8 in CSF was examined.
Measured: Baseline, Month 8
Interleukin-9 (IL-9) Frequency
The inflammatory marker IL-9 in CSF was examined.
Measured: Baseline, Month 8
Interleukin-10 (IL-10) Frequency
The inflammatory marker IL-10 in CSF was examined.
Measured: Baseline, Month 8
Monocyte Chemoattractant Protein 1 (MCP-1) Frequency
Monocyte chemoattractant protein 1 inflammatory markers in CSF were examined.
Measured: Baseline, Month 8
Macrophage Derived Protein 1 (MDC-1) Frequency
Macrophage derived protein 1 inflammatory markers in CSF were examined.
Measured: Baseline, Month 8
Transforming Growth Factor Alpha (TGF-α) Frequency
Transforming growth factor alpha inflammatory markers in CSF were examined.
Measured: Baseline, Month 8
Tumor Necrosis Factor Alpha (TNF-α) Frequency
Tumor necrosis factor alpha inflammatory markers in CSF were examined.
Measured: Baseline, Month 8
Intercellular Adhesion Molecule 1 (ICAM-1) Frequency
Intercellular adhesion molecule 1 inflammatory markers in CSF were examined.
Measured: Baseline, Month 8
Vascular Cell Adhesion Molecule 1 (VCAM-1) Frequency
Vascular cell adhesion molecule 1 inflammatory markers in CSF were examined.
Measured: Baseline, Month 8
Matrix Metalloproteinase (MMP) Frequency
Matrix metalloproteinase inflammatory markers will be examined in CSF.
Measured: Baseline, Month 8
Tissue Inhibitor of Metalloproteinase (TIMP) Frequency
Tissue inhibitor of metalloproteinase inflammatory markers will be examined in CSF.
Measured: Baseline, Month 8
CSF-Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ)
Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ) is a marker of breakdown in the blood brain barrier. Increased levels of sPDGFRβ indicate cognitive dysfunction.
Measured: Baseline, Month 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startApr 2015
- Primary completion15 Apr 2022
- Study completion15 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Whitney Wharton, Emory University
- Investigators
- Whitney Whitney, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02471833
- Sponsor's protocol ID
- IRB00080192
- Other IDs
- 1RF1AG051514
- Acronym
- HEART
- Status last verified
- Apr 2024
- First submitted
- 10 Jun 2015
- Last updated
- 23 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wharton W, Goldstein FC, Tansey MG, Brown AL, Tharwani SD, Verble DD, Cintron A, Kehoe PG. Rationale and Design of the Mechanistic Potential of Antihypertensives in Preclinical Alzheimer's (HEART) Trial. J Alzheimers Dis. 2018;61(2):815-824. doi: 10.3233/JAD-161198.
PubMed 29254080
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Health Evaluation in African Americans Using RAS Therapy
- ClinicalTrials.gov ID
- NCT02471833
- Acronym / sponsor ID
- HEART / IRB00080192
- Conditions
- Alzheimer's Disease
- Keywords
- hypertension, prevention, family history, inflammation, blood brain barrier, amyloid
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Apr 2015 (actual)
- Primary completion
- 15 Apr 2022 (actual)
- Study completion
- 15 Apr 2022 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Posted 23 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease prevention in African Americans, who are at high risk for Alzheimer's disease.
Detailed description
This study will assess if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease (AD) prevention in African Americans, who are at high risk for Alzheimer's disease. Blood pressure medications known as angiotensin-receptor blockers have been associated with reduced risk of Alzheimer's in Caucasians because they act on the renin-angiotensin system (RAS), a key regulator of blood pressure in the body and the brain. The drugs appear to slow the progression of the disease by affecting flow of blood and the amount of plaque in the brain, but these benefits have not been tested in African Americans. The investigator will evaluate if telmisartan is able to influence the renin-angiotensin system in the brain and produce favorable effects on brain blood flow and enzymes that cause the brain plaques in Alzheimer's disease.The investigator will assess the mechanism by which telmisartan modifies the brain renin angiotensin system, cerebrospinal fluid amyloid-β, cerebral blood flow (CBF) and inflammatory markers in hypertensive African Americans.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Telmisartan 20mg | Experimental | Drug: Telmisartan 20mgAfrican American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive telmisartan 20mg once a day orally. |
| Telmisartan 40mg | Experimental | Drug: Telmisartan 40mgAfrican American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive telmisartan 40mg once a day orally. |
| Placebo | Placebo comparator | Drug: PlaceboAfrican American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive a placebo to match telmisartan once a day orally. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Mean resting systolic blood pressure ≥ 110 mmHg and ≤ 170 mmHg
- Family history of Alzheimer's disease
- African American
Key exclusion criteria (10 listed)
- Currently in another investigational drug study
- Potassium >5.0 meq/dL at baseline
- Creatinine >1.99 mg/dL at baseline
- History of stroke or transient ischemic attack (TIA)
- Dementia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telmisartan 20mgAlso: MicardisParticipants will be given 20 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months. | Drug | Telmisartan 20mg |
| Telmisartan 40mgAlso: MicardisParticipants will be given 40 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months. | Drug | Telmisartan 40mg |
| PlaceboParticipants will be given placebo to be taken orally once a day before bedtime, for a duration of 8 months. | Drug | Placebo |
Primary outcome
Concentration of Angiotensin Converting Enzyme (ACE 1)
Time frame: Baseline, Month 8
The cerebrospinal fluid renin-angiotensin system (RAS) was assessed by measuring levels of angiotensin metabolites in a 1 milliliter (mL) sample of cerebrospinal fluid (CSF). ACE 1 helps to regulate blood pressure by converting angiotensin I to angiotensin II.
Concentration of Angiotensin Converting Enzyme 2 (ACE 2)
Time frame: Baseline, Month 8
The cerebrospinal fluid renin-angiotensin system (RAS) was assessed by measuring levels of angiotensin metabolites in a 1 milliliter (mL) sample of cerebrospinal fluid (CSF). ACE 2 regulates levels of circulating angiotensin II. ACE 2 increases during illness and with Alzheimer's disease.
Cerebrospinal Fluid Amyloid β40
Time frame: Baseline, Month 8
Levels of amyloid β40 (Aβ40) in the cerebrospinal fluid were measured using LUMIPULSE® technology. The relationship between Aβ40 is non-linear with moderate levels showing the highest risk of future cognitive decline in some studies.
Levels of Cerebrospinal Fluid Amyloid β42
Time frame: Baseline, Month 8
Levels of amyloid β42 (Aβ42) in the cerebrospinal fluid were measured using LUMIPULSE® technology. Decreases in concentrations of amyloid β42 are indicative of a decrease in cognitive function.
Levels of Cerebrospinal Fluid T-tau
Time frame: Baseline, Month 8
Levels of T-tau in the cerebrospinal fluid were measured using LUMIPULSE® technology. Increases in concentrations of T-tau are indicative of a decrease in cognitive function.
Levels of Cerebrospinal Fluid P-tau
Time frame: Baseline, Month 8
Levels of P-tau in the cerebrospinal fluid were measured using LUMIPULSE® technology. Increases in concentrations of P-tau are indicative of a decrease in cognitive function.
14 secondary outcomes
Interleukin-6 (IL-6) Frequency
Time frame: Baseline, Month 8
Interleukin-7 (IL-7) Frequency
Time frame: Baseline, Month 8
Interleukin-8 (IL-8) Frequency
Time frame: Baseline, Month 8
Interleukin-9 (IL-9) Frequency
Time frame: Baseline, Month 8
Interleukin-10 (IL-10) Frequency
Time frame: Baseline, Month 8
Monocyte Chemoattractant Protein 1 (MCP-1) Frequency
Time frame: Baseline, Month 8
Macrophage Derived Protein 1 (MDC-1) Frequency
Time frame: Baseline, Month 8
Transforming Growth Factor Alpha (TGF-α) Frequency
Time frame: Baseline, Month 8
Tumor Necrosis Factor Alpha (TNF-α) Frequency
Time frame: Baseline, Month 8
Intercellular Adhesion Molecule 1 (ICAM-1) Frequency
Time frame: Baseline, Month 8
Vascular Cell Adhesion Molecule 1 (VCAM-1) Frequency
Time frame: Baseline, Month 8
Matrix Metalloproteinase (MMP) Frequency
Time frame: Baseline, Month 8
Tissue Inhibitor of Metalloproteinase (TIMP) Frequency
Time frame: Baseline, Month 8
CSF-Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ)
Time frame: Baseline, Month 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29254080Wharton W, Goldstein FC, Tansey MG, Brown AL, Tharwani SD, Verble DD, Cintron A, Kehoe PG. Rationale and Design of the Mechanistic Potential of Antihypertensives in Preclinical Alzheimer's (HEART) Trial. J Alzheimers Dis. 2018;61(2):815-824. doi: 10.3233/JAD-161198.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Whitney Whitney, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Telmisartan 20mg and Telmisartan 40mg in people with Alzheimer's Disease, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of Angiotensin Converting Enzyme (ACE 1) (time frame: Baseline, Month 8). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02471833, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.