HypertensionEarly Phase 1NCT02744456
N-of-1 Trials for Blood Pressure Medications in Adults
A Early Phase 1 study testing Losartan, Amlodipine and Hydrochlorothiazide in people with Hypertension and High Blood Pressure, run by Columbia University at 1 site in United States.
Trial summary
Many patients want to know which blood pressure medication is the best for them. In this study, we will test the feasibility of a new approach to determining the best blood pressure medication for individual patients by performing an N-of-1 trial in which patients will have the opportunity to test a series of 3 blood… Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Hypertension, High Blood Pressure
- What is being tested?
- Losartan, Amlodipine and Hydrochlorothiazide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2014to 31 Dec 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 21 to 80 years.
- History of physician-diagnosed hypertension.
- Currently not treated with antihypertensive medication but with consensus (from patient and his/her physician; patients with elevated ABPM who are not on treatment will be considered eligible irrespective of office BP if the patient's physician is in agreement with a trial of BP medications) that antihypertensive medication should be initiated; or being treated with one antihypertensive medication.
- No history of suspected or confirmed white coat hypertension (elevated clinic BP but non-elevated out-of-clinic BP either by home BP monitoring or ABPM).
- Easy access to and regular use of e-mail as they will need to be able to respond to Qualtrics surveys at regular intervals during the self-monitoring period.
- Established relationship with an accessible primary care provider.
- Primary care provider gives permission to participation in an N-of-1 trial.
Who cannot join
- Severe hypertension (office BP = 180/110 mm Hg).
- History of myocardial infarction, heart failure, atrial fibrillation, or chronic kidney disease as these patients have guideline recommended indications for specific classes of BP medications.
- Electrolyte abnormality; if no electrolyte panel is available in the prior 6 months, then one will be ordered for purposes of the study.
- Known drug allergy or intolerance to angiotensin receptor blocker, calcium channel blocker, or thiazide diuretic.
- Prescribed BP medication for indication other than hypertension (e.g., migraine headache prophylaxis, enlarged prostate).
- Primary care provider permission not obtained.
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- Non-English speaking.
- No regular (daily) access and use of e-mail as participants will need to be able to respond to emailed links to surveys for completion of self-monitoring symptoms.
- Unable to provide informed consent or adhere to study protocol due to cognitive impairment, mental illness, or other reasons.
- Unable to monitor BP at home using an automatic BP machine due to physical or mental impairments.
- Unable to track side effects of medications due to physical or mental impairments including literacy problems.
- Arm circumference <9 inches or >17 inches as these sizes do not accommodate the range of BP cuff sizes that are available for the automatic BP machine.
- Unavailable for follow-up during the study period due to severe medical illness or other reasons.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: A Pilot Study of N-of-1 Trials of Blood Pressure Medications in Adults With Hypertension
Many patients want to know which blood pressure medication is the best for them. In this study, we will test the feasibility of a new approach to determining the best blood pressure medication for individual patients by performing an N-of-1 trial in which patients will have the opportunity to test a series of 3 blood pressure medications at escalating doses while carefully measuring their blood pressure and side-effects. At the end of each of these N-of-1 trials, we will ask patients to complete a questionnaire in which they rate their level of satisfaction with this approach to learning about which is the best blood pressure medication for them.
Read the detailed description
The goal of this research is to empower hypertensive patients to learn which blood pressure (BP) medication is best for them. Although lifestyle factors such as diet and exercise play an important role, medications may still needed to achieve BP control. Yet, there are substantial differences in the way BP medications affect patients; medications well-tolerated in some, cause severe side-effects in others. Similarly, medications that cause larger reductions in BP in some patients have smaller BP lowering effects in others. Despite this heterogeneity in treatment effects, there are no proven real-world methods to help patients identify the medication most suited to their needs.
One potential approach to individualizing BP treatment decisions is to conduct N-of-1 trials: a multiple crossover design conducted in a single patient. Despite the appeal of this approach, there are few published reports of BP medication N-of-1 trials. Therefore, the objective of this study is to determine the feasibility of conducting an N-of-1 BP medication trial in hypertensive patients. Patients who meet all the eligibility criteria will be asked to monitor their blood pressure and side-effects while taking a series of commonly prescribed blood pressure medications. If they are already taking a blood pressure medication, they will begin by tracking their blood pressure and side-effects while taking this medication for 1 week. They will then be asked to track their blood pressure and side-effects while taking a series of up to three other blood pressure medications (losartan - a renin-angiotensin system blocking agent, amlodipine - a calcium channel blocker, and hydrochlorothiazide - a thiazide diuretic). Each of these medications will be taken for 2 weeks at a time. The specific choice of medications and medication doses will be selected by the study physician. Unless patients have side-effects that lead them to discontinue a medication early, patients will be expected to take each medication at least twice in a balanced sequence (e.g., losartan - amlodipine - HCTZ - HCTZ - amlodipine - losartan). Patients will measure their blood pressure and medication side-effects during the 2nd week on each of these medications. Patients will have the option of escalating or decreasing dosages to identify the single medication/medication dose that best lowers their blood pressure with the least side-effects. Blood pressure will be measured using an Omron home blood pressure monitor. Side-effects will be tracked using a daily e-mailed survey that is completed over the Internet.
- Conditions
- Hypertension, High Blood Pressure
- Being tested
- Losartan, Amlodipine, Hydrochlorothiazide
- Keywords
- Hydrochlorothiazide tablet, Norvasc, Cozaar, amlodipine besylate tablets, losartan potassium tablets, Hypertension, High Blood Pressure
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Losartan potassium tablets, Cozaar
An angiotensin II receptor antagonist drug used mainly to treat high blood pressure.
AmlodipineDrug
Also called Amlodipine besylate tablets, Norvasc
A calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of hypertension.
HydrochlorothiazideDrug
Also called HCTZ, Hydrochlorothiazide tablets
A diuretic medication often used to treat high blood pressure and swelling due to fluid build up.
| Study group | Role | What they receive |
|---|---|---|
| N-of-1 trial | Other | Patients with hypertension who are taking none or one BP medication will be will be provided with prescriptions for up to 3 BP medications representative of different BP medication classes (i.e., losartan, an angiotensin system blocking agent; amlodipine, a calcium channel blocker; and hydrochlorothiazide, a thiazide diuretic). Patients will be asked to take each medication for 2 weeks at a low dose, 2 weeks at a medium dose, and then 2 weeks at a high dose; provide health information and identify which medication they prefer to remain on following the N-of-1 trial (i.e., for long-term use). Receives: Drug: Losartan; Drug: Amlodipine; Drug: Hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants satisfied with participating in N-of-1 trial
Question assessing helpfulness of participating in N-of-1 trial methodology with respecting to managing their hypertension
Measured: 4 months
Secondary outcomes (1)
Participants satisfied with blood pressure regimen
Treatment Satisfaction Questionnaire for Medication
Measured: 5 months (or 1 month after completing N-of-1 trial)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2016 (estimated)
- Study start1 Aug 2014
- Primary completion31 Aug 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Columbia 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ian Kronish, Columbia University
- Investigators
- Ian Kronish, MD, MPH, Principal investigator, Columbia Univeristy Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02744456
- Sponsor's protocol ID
- AAAN9419
- Status last verified
- Mar 2019
- First submitted
- 13 Apr 2016
- Last updated
- 26 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: IPD is currently presented in the manuscript due to the N-of-1 study design. Participant consent forms will be reviewed with the Columbia University IRB to determine whether we have permission to share de-identified IPD with other researchers.
Publications
Kronish IM, Cheung YK, Shimbo D, Julian J, Gallagher B, Parsons F, Davidson KW. Increasing the Precision of Hypertension Treatment Through Personalized Trials: a Pilot Study. J Gen Intern Med. 2019 Jun;34(6):839-845. doi: 10.1007/s11606-019-04831-z. Epub 2019 Mar 11.
PubMed 30859504
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of N-of-1 Trials of Blood Pressure Medications in Adults With Hypertension
- ClinicalTrials.gov ID
- NCT02744456
- Acronym / sponsor ID
- AAAN9419
- Conditions
- Hypertension, High Blood Pressure
- Keywords
- Hydrochlorothiazide tablet, Norvasc, Cozaar, amlodipine besylate tablets, losartan potassium tablets, Hypertension, High Blood Pressure
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 1 Aug 2014 (actual)
- Primary completion
- 31 Aug 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 20 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many patients want to know which blood pressure medication is the best for them. In this study, we will test the feasibility of a new approach to determining the best blood pressure medication for individual patients by performing an N-of-1 trial in which patients will have the opportunity to test a series of 3 blood pressure medications at escalating doses while carefully measuring their blood pressure and side-effects. At the end of each of these N-of-1 trials, we will ask patients to complete a questionnaire in which they rate their level of satisfaction with this approach to learning about which is the best blood pressure medication for them.
Detailed description
The goal of this research is to empower hypertensive patients to learn which blood pressure (BP) medication is best for them. Although lifestyle factors such as diet and exercise play an important role, medications may still needed to achieve BP control. Yet, there are substantial differences in the way BP medications affect patients; medications well-tolerated in some, cause severe side-effects in others. Similarly, medications that cause larger reductions in BP in some patients have smaller BP lowering effects in others. Despite this heterogeneity in treatment effects, there are no proven real-world methods to help patients identify the medication most suited to their needs.
One potential approach to individualizing BP treatment decisions is to conduct N-of-1 trials: a multiple crossover design conducted in a single patient. Despite the appeal of this approach, there are few published reports of BP medication N-of-1 trials. Therefore, the objective of this study is to determine the feasibility of conducting an N-of-1 BP medication trial in hypertensive patients. Patients who meet all the eligibility criteria will be asked to monitor their blood pressure and side-effects while taking a series of commonly prescribed blood pressure medications. If they are already taking a blood pressure medication, they will begin by tracking their blood pressure and side-effects while taking this medication for 1 week. They will then be asked to track their blood pressure and side-effects while taking a series of up to three other blood pressure medications (losartan - a renin-angiotensin system blocking agent, amlodipine - a calcium channel blocker, and hydrochlorothiazide - a thiazide diuretic). Each of these medications will be taken for 2 weeks at a time. The specific choice of medications and medication doses will be selected by the study physician. Unless patients have side-effects that lead them to discontinue a medication early, patients will be expected to take each medication at least twice in a balanced sequence (e.g., losartan - amlodipine - HCTZ - HCTZ - amlodipine - losartan). Patients will measure their blood pressure and medication side-effects during the 2nd week on each of these medications. Patients will have the option of escalating or decreasing dosages to identify the single medication/medication dose that best lowers their blood pressure with the least side-effects. Blood pressure will be measured using an Omron home blood pressure monitor. Side-effects will be tracked using a daily e-mailed survey that is completed over the Internet.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N-of-1 trial | Other | Drug: Losartan, Drug: Amlodipine, Drug: HydrochlorothiazidePatients with hypertension who are taking none or one BP medication will be will be provided with prescriptions for up to 3 BP medications representative of different BP medication classes (i.e., losartan, an angiotensin system blocking agent; amlodipine, a calcium channel blocker; and hydrochlorothiazide, a thiazide diuretic). Patients will be asked to take each medication for 2 weeks at a low dose, 2 weeks at a medium dose, and then 2 weeks at a high dose; provide health information and identify which medication they prefer to remain on following the N-of-1 trial (i.e., for long-term use). |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 21 to 80 years.
- History of physician-diagnosed hypertension.
- Currently not treated with antihypertensive medication but with consensus (from patient and his/her physician; patients with elevated ABPM who are not on treatment will be considered eligible irrespective of office BP if the patient's physician is in agreement with a trial of BP medications) that antihypertensive medication should be initiated; or being treated with one antihypertensive medication.
- No history of suspected or confirmed white coat hypertension (elevated clinic BP but non-elevated out-of-clinic BP either by home BP monitoring or ABPM).
- Easy access to and regular use of e-mail as they will need to be able to respond to Qualtrics surveys at regular intervals during the self-monitoring period.
Key exclusion criteria (13 listed)
- Severe hypertension (office BP = 180/110 mm Hg).
- History of myocardial infarction, heart failure, atrial fibrillation, or chronic kidney disease as these patients have guideline recommended indications for specific classes of BP medications.
- Electrolyte abnormality; if no electrolyte panel is available in the prior 6 months, then one will be ordered for purposes of the study.
- Known drug allergy or intolerance to angiotensin receptor blocker, calcium channel blocker, or thiazide diuretic.
- Prescribed BP medication for indication other than hypertension (e.g., migraine headache prophylaxis, enlarged prostate).
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 |
|---|---|---|
| LosartanAlso: Losartan potassium tablets, CozaarAn angiotensin II receptor antagonist drug used mainly to treat high blood pressure. | Drug | N-of-1 trial |
| AmlodipineAlso: Amlodipine besylate tablets, NorvascA calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of hypertension. | Drug | N-of-1 trial |
| HydrochlorothiazideAlso: HCTZ, Hydrochlorothiazide tabletsA diuretic medication often used to treat high blood pressure and swelling due to fluid build up. | Drug | N-of-1 trial |
Primary outcome
Participants satisfied with participating in N-of-1 trial
Time frame: 4 months
Question assessing helpfulness of participating in N-of-1 trial methodology with respecting to managing their hypertension
1 secondary outcome
Participants satisfied with blood pressure regimen
Time frame: 5 months (or 1 month after completing N-of-1 trial)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Derived from this study: PubMed 30859504Kronish IM, Cheung YK, Shimbo D, Julian J, Gallagher B, Parsons F, Davidson KW. Increasing the Precision of Hypertension Treatment Through Personalized Trials: a Pilot Study. J Gen Intern Med. 2019 Jun;34(6):839-845. doi: 10.1007/s11606-019-04831-z. Epub 2019 Mar 11.
- Individual participant dataSharing planned: Undecided. IPD is currently presented in the manuscript due to the N-of-1 study design. Participant consent forms will be reviewed with the Columbia University IRB to determine whether we have permission to share de-identified IPD with other researchers.
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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.
Ian Kronish, MD, MPH principal investigator
Columbia Univeristy Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Losartan, Amlodipine and Hydrochlorothiazide in people with Hypertension and High Blood Pressure, run by Columbia 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 7 inclusion and 13 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 26 Mar 2019. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Participants satisfied with participating in N-of-1 trial (time frame: 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 NCT02744456, 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 26 Mar 2019.