Alzheimer's DiseasePhase 4SEAIRANCT00980785
Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's
A Phase 4 study testing Ramipril in people with Alzheimer's Disease and Hypertension, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Angiotensin converting enzyme inhibitors (ACE-I) are a group of blood pressure-lowering medicines. Some studies suggest that ACE-I, such as ramipril, may help prevent Alzheimer's disease (AD). The purpose of the research is to see how ramipril affects a substance in the body called beta-amyloid. Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease, Hypertension
- What is being tested?
- Ramipril
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Apr 2009to 26 Jul 2011
- Phase
- Phase 4
- 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 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Between the ages of 40 and 65
- Mean resting blood pressure between 130-160 systolic and 85-100 diastolic
- Parent with Alzheimer's Disease
Who cannot join
- Current involvement in another investigational drug trial.
- Potassium > 5.0
- Dementia based on DSMIV criteria
- Mini-Mental State Exam (MMSE) score < 27
- Current blood pressure medication (< 4 months from screening)
- Weight loss medication
Show all 12Show fewer
- Contraindications for LP
- Know diagnosis or history of hospitalization due to congestive heart failure
- Elevated creatinine (females > 1.3 mg/dL or males > 1.4 mg/dL at baseline)
- Diabetes Type I and II
- Know adverse reaction to an ACE-I or an angiotensin receptor blocker
- Pregnant of nursing women
Trial locations and contacts
1 site in 1 country.
United States1 site
Wisconisn Alzheimer's Disease Research Center
Madison, Wisconsin, 53705
About this study
Angiotensin converting enzyme inhibitors (ACE-I) are a group of blood pressure-lowering medicines. Some studies suggest that ACE-I, such as ramipril, may help prevent Alzheimer's disease (AD). The purpose of the research is to see how ramipril affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal cord. High amounts of beta-amyloid may be associated with a greater risk of getting Alzheimer's disease. This study will see if ramipril can lower the amount of beta-amyloid in the spinal fluid. This study will also see if ramipril affects blood vessel function and memory and thinking. The investigators hope that future studies will show whether ramipril might prevent memory loss and decrease the chance of developing Alzheimer's disease.
Read the detailed description
High blood pressure (BP) in midlife is predictive of Alzheimer's disease (AD) in later life. Similarly, reductions in BP are associated with protection against AD. Treatment with antihypertensive medications, specifically angiotensin converting enzyme inhibitors (ACE-I) such as ramipril, is associated with up to a 55% reduction in the prevalence of AD, suggesting a potentially promising role for ACE-I in the prevention of AD. It is unknown however 1) whether ACE-Is will have the same effect on Cerebrospinal fluid (CSF) Aβ levels in humans as in animal models 2) whether ACE-Is induce changes associated with vascular function (i.e. levels of CSF angiotensin converting enzyme (ACE) and peripheral endothelial function) and 3) whether there are interactions between ACE-I-induced changes in CSF Aβ, CSF ACE and indices of vascular function.
One mechanism by which antihypertensives may protect against AD is via Aβ neuropathology. In order to better understand the mechanisms through which ACE-I may modify CSF Aβ and possibly AD risk, we propose a randomized, double-blind, placebo-controlled pilot clinical trial, enrolling 20 middle-aged (age range 40 - 65 years), mildly hypertensive (between 130 - 160 mmHg mean systolic and between 85 - 100 mmHg mean diastolic) participants, who are adult children of an individual with AD. The main objective of this trial is to examine the effects of the ACE-I, ramipril, on 1) CSF Aβ levels 2) CSF ACE levels and 3) peripheral endothelial function as measured by brachial artery flow-mediated vasodilation (FMD) and aortic augmentation index (AAIx), in middle-aged adults with mildly elevated BP, who are at increased risk of developing AD.
- Conditions
- Alzheimer's Disease, Hypertension
- Being tested
- Ramipril, Placebo
- Keywords
- Alzheimer's Disease, Hypertension
- Medical subject headings
- Alzheimer Disease, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamiprilDrug
Also called Altace
Ramipril 5 mg/day
PlaceboDrug
Matching Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching Placebo Receives: Drug: Placebo |
| Active | Experimental | Ramipril 5mg/day Receives: Drug: Ramipril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cerebrospinal Fluid (CSF) Amyloid Beta-42 (Aβ42) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
CSF Aβ42 levels will be measured from the cerebrospinal fluid taken from subjects on ramipril or placebo at the baseline visit and month 4 and will be measured by Dr. Henrik Zetterberg's laboratory.
Measured: Baseline to 4 months
Secondary outcomes (3)
Change in CSF Angiotensin Converting Enzyme (ACE) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
CSF ACE levels will be measured from the cerebrospinal fluid taken from subjects on Ramipril or placebo at the baseline visit and month 4 and will be measured by ARUP® laboratories by spectrophotometric enzymatic assay.
Measured: Baseline to 4 months
Change in Flow-mediated Vasodilation (FMD) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
FMD is calculated as the ratio of brachial artery diameter after reactive hyperemia to baseline diameter, expressed as percentage change. FMD for each subject (ramipril v placebo) will be measured at baseline and month 4, observing any differences.
Measured: Baseline to 4 months
Change in Augmentation Index (%) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Pulse wave velocity was measured using an AtCor SphymoCor Px tonometry system. A small pressure transducer was placed on the skin at the point the arterial pulsation of the right common carotid and right radial arteries. A Millar micromanometer is in the tip of the probe. Using a generalized transfer function, the distance between these pressure points, and the peripheral arterial waveforms, a central aortic pressure signal is derived, from which aortic augmentation index is determined.
Measured: Baseline to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2009 (estimated)
- Study start9 Apr 2009
- Primary completion26 Jul 2011
- Study completion26 Jul 2011
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 University of Wisconsin, MadisonThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cynthia M Carlsson, MD, MS, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00980785
- Sponsor's protocol ID
- 2014-1353
- Other IDs
- H-2009-0036, A534255, SMPH/MEDICINE/GER-AD DEV
- Acronym
- SEAIRA
- Status last verified
- Aug 2020
- First submitted
- 18 Sep 2009
- Last updated
- 25 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wharton W, Stein JH, Korcarz C, Sachs J, Olson SR, Zetterberg H, Dowling M, Ye S, Gleason CE, Underbakke G, Jacobson LE, Johnson SC, Sager MA, Asthana S, Carlsson CM. The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial. J Alzheimers Dis. 2012;32(1):147-56. doi: 10.3233/JAD-2012-120763.
PubMed 22776970
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's
- ClinicalTrials.gov ID
- NCT00980785
- Acronym / sponsor ID
- SEAIRA / 2014-1353
- Conditions
- Alzheimer's Disease, Hypertension
- Keywords
- Alzheimer's Disease, Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- 9 Apr 2009 (actual)
- Primary completion
- 26 Jul 2011 (actual)
- Study completion
- 26 Jul 2011 (actual)
- First posted
- 21 Sep 2009 (estimated)
- Results
- Posted 25 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Angiotensin converting enzyme inhibitors (ACE-I) are a group of blood pressure-lowering medicines. Some studies suggest that ACE-I, such as ramipril, may help prevent Alzheimer's disease (AD). The purpose of the research is to see how ramipril affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal cord. High amounts of beta-amyloid may be associated with a greater risk of getting Alzheimer's disease. This study will see if ramipril can lower the amount of beta-amyloid in the spinal fluid. This study will also see if ramipril affects blood vessel function and memory and thinking. The investigators hope that future studies will show whether ramipril might prevent memory loss and decrease the chance of developing Alzheimer's disease.
Detailed description
High blood pressure (BP) in midlife is predictive of Alzheimer's disease (AD) in later life. Similarly, reductions in BP are associated with protection against AD. Treatment with antihypertensive medications, specifically angiotensin converting enzyme inhibitors (ACE-I) such as ramipril, is associated with up to a 55% reduction in the prevalence of AD, suggesting a potentially promising role for ACE-I in the prevention of AD. It is unknown however 1) whether ACE-Is will have the same effect on Cerebrospinal fluid (CSF) Aβ levels in humans as in animal models 2) whether ACE-Is induce changes associated with vascular function (i.e. levels of CSF angiotensin converting enzyme (ACE) and peripheral endothelial function) and 3) whether there are interactions between ACE-I-induced changes in CSF Aβ, CSF ACE and indices of vascular function.
One mechanism by which antihypertensives may protect against AD is via Aβ neuropathology. In order to better understand the mechanisms through which ACE-I may modify CSF Aβ and possibly AD risk, we propose a randomized, double-blind, placebo-controlled pilot clinical trial, enrolling 20 middle-aged (age range 40 - 65 years), mildly hypertensive (between 130 - 160 mmHg mean systolic and between 85 - 100 mmHg mean diastolic) participants, who are adult children of an individual with AD. The main objective of this trial is to examine the effects of the ACE-I, ramipril, on 1) CSF Aβ levels 2) CSF ACE levels and 3) peripheral endothelial function as measured by brachial artery flow-mediated vasodilation (FMD) and aortic augmentation index (AAIx), in middle-aged adults with mildly elevated BP, who are at increased risk of developing AD.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMatching Placebo |
| Active | Experimental | Drug: RamiprilRamipril 5mg/day |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Between the ages of 40 and 65
- Mean resting blood pressure between 130-160 systolic and 85-100 diastolic
- Parent with Alzheimer's Disease
Key exclusion criteria (12 listed)
- Current involvement in another investigational drug trial.
- Potassium > 5.0
- Dementia based on DSMIV criteria
- Mini-Mental State Exam (MMSE) score < 27
- Current blood pressure medication (< 4 months from screening)
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 |
|---|---|---|
| RamiprilAlso: AltaceRamipril 5 mg/day | Drug | Active |
| PlaceboMatching Placebo | Drug | Placebo |
Primary outcome
Change in Cerebrospinal Fluid (CSF) Amyloid Beta-42 (Aβ42) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time frame: Baseline to 4 months
CSF Aβ42 levels will be measured from the cerebrospinal fluid taken from subjects on ramipril or placebo at the baseline visit and month 4 and will be measured by Dr. Henrik Zetterberg's laboratory.
3 secondary outcomes
Change in CSF Angiotensin Converting Enzyme (ACE) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time frame: Baseline to 4 months
Change in Flow-mediated Vasodilation (FMD) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time frame: Baseline to 4 months
Change in Augmentation Index (%) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time frame: Baseline to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22776970Wharton W, Stein JH, Korcarz C, Sachs J, Olson SR, Zetterberg H, Dowling M, Ye S, Gleason CE, Underbakke G, Jacobson LE, Johnson SC, Sager MA, Asthana S, Carlsson CM. The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial. J Alzheimers Dis. 2012;32(1):147-56. doi: 10.3233/JAD-2012-120763.
- Related InfoLink provided by the sponsor.
- The Effects of Ramipril in Individuals at Risk for Alzheimer's Disease: Results of a Pilot Clinical TrialLink provided by the sponsor.
Related trials for Alzheimer's Disease
RecruitingPhase 3
Nabilone for Agitation Blinded Intervention Trial
Alzheimer Disease, Agitation
Active, not recruitingPhase 2
A Study to Evaluate the Safety and Biomarker Effects of RO7269162 in Participants at Risk for or at the Prodromal Stage of Alzheimer's Disease (AD)
Alzheimer's Disease
Recruiting
HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms
Alzheimer Disease, Dementia
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingObservational study
PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)
Aging
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.
Cynthia M Carlsson, MD, MS principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ramipril in people with Alzheimer's Disease and Hypertension, run by University of Wisconsin, Madison 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 12 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 25 Aug 2020. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 25 Aug 2020). 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?
Change in Cerebrospinal Fluid (CSF) Amyloid Beta-42 (Aβ42) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo (time frame: Baseline to 4 months). 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 NCT00980785, 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 25 Aug 2020; AzTrials last refreshed its copy on 8 Nov 2026.