HypertensionINTREPIDNCT05976438
Skin Sodium and Salt Sensitivity of Blood Pressure
A study testing Amlodipine and Chlortalidone in people with Hypertension, run by Cambridge University Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
Eating too much salt raises blood pressure and the risk of having a heart attack or stroke. The investigators do not fully understand why salt raises blood pressure, but storage of sodium in the body, particularly in the skin, may be important. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Amlodipine and Chlortalidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Aug 2023to Dec 2024
- Phase
- Interventional
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have given written informed consent to participate
- Aged 18 or above
- Be hypertensive defined as:
- Currently untreated with an ABPM day time average blood pressure or average home blood pressure of ≥135 mmHg (systolic) or ≥85 mmHg (diastolic)
- OR
- Patients who are taking antihypertensive drugs at sub therapeutic doses or in ineffective combinations, and who are felt likely to be controllable on a study drug and willing and able to be washed out, at the discretion of the CI/PI, can enter the study if they meet the above criteria.
Who cannot join
- Uncontrolled blood pressure ≥ 180/110mmHg
- Known or suspected secondary hypertension
- Pregnant or breastfeeding women
- Significant sensitivity or contraindications to any of the study medications
- Participants taking lithium or are regularly consuming non-steroidal anti-inflammatory drugs at variable doses
- Requirement to take any of the study drugs continuously e.g. ACEi and heart failure
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- Any clinically significant hepatic impairment
- Any clinically significant kidney impairment
- Concurrent participation in another clinical trial or study using systemic vasoactive medications or medications known to interact with the study drugs
- Patients who are deemed unsuitable by the investigator on clinical grounds e.g. an abnormal heart rhythm due to Atrial Fibrillation (AF)
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Addenbrooke's Hospital
Cambridge
Irene Sambath, cuh.intrepid@nhs.net
St Thomas' Hospital
London
Luca Faconti
About this study
Official title: Investigating the Relevance of Skin Sodium and Salt Sensitivity of Blood Pressure in Determining the Response to Anti-Hypertensive Drugs (INTREPID)
Eating too much salt raises blood pressure and the risk of having a heart attack or stroke. The investigators do not fully understand why salt raises blood pressure, but storage of sodium in the body, particularly in the skin, may be important. For this reason, the investigators wish to study the link between skin sodium, blood pressure and cardiovascular risk in patients with high blood pressure, of different ethnicities, using techniques such as skin biopsy and magnetic resonance imaging (MRI). The results will provide detailed information on skin sodium storage and help us better understand the effects of blood pressure medications on these mechanisms. Ultimately, the investigators aim to develop personalized treatment guidelines for clinical use.
Read the detailed description
The physiological basis of salt sensitivity of blood pressure (SSBP) is poorly understood, and determining which patients have SSBP is not straightforward. Furthermore, determining salt sensitivity requires direct intervention tracking changes in blood pressure after salt challenge or depletion over several days. This makes identifying salt-sensitive individuals impractical in a clinical setting, hindering its application. It is crucial that the investigators elucidate the underlying mechanisms of salt-sensitivity, and through this understanding develop a biomarker of SSBP for clinical use.
From a review of recent studies it appears that in the short-term, accumulation of skin sodium during high salt intake attenuates the blood pressure response, while in the long-term, high skin sodium levels indicate a tendency for SSBP, hypertension and elevated cardiovascular risk. The reasons for this are not clear and merit further investigation. By refining methods for quantification of skin sodium and expanding its use in hypertension research, the clinicians can improve patient assessment, treatment prescription, and disease monitoring.
Using skin biopsy and sodium MRI provides a unique opportunity to study skin sodium handling and SSBP during antihypertensive treatment, and can provide insights into why hypertensives and certain ethnic groups have a higher incidence of SSBP. Sodium MRI may also help increase our understanding of the mechanisms by which diuretics work, both systemically and in the kidney and provide a way to identify salt-sensitive individuals for targeted clinical intervention.
Hypotheses:
- Skin sodium decreases with salt-dependent (diuretic) treatments but not salt-independent (calcium channel blocker) treatments.
- Diuretic-induced reductions in skin sodium correlate with reductions in blood pressure.
- Skin sodium is higher in populations traditionally known to be more salt sensitive, such hypertensive patients of black ethnicity.
Patients will be enrolled on to a randomised, open-label, two-treatment two-period crossover treatment. The hypertensive medication used in this study are Amlodipine 5 or 10mg and Chlortalidone 25mg.
The duration for individual participants will be approximately 16 weeks. Participants will have a total of 7 visits including screening/enrolment (visit 1) and baseline visit (visit 2).
- Conditions
- Hypertension
- Being tested
- Amlodipine, Chlortalidone
- Keywords
- Skin Sodium, Salt Sensitivity, Blood Pressure, Heart Disease, Cardiovascular
- Medical subject headings
- Hypertension, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmlodipineDrug
Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.
ChlortalidoneDrug
Chlortalidone 25mg will be one of the study drugs the patients will receive.
| Study group | Role | What they receive |
|---|---|---|
| Open label arm 1 | Other | Participants will be randomised to AB sequence of drugs A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg B: Approximately 8 weeks of 25mg Chlortalidone Receives: Drug: Amlodipine; Drug: Chlortalidone |
| Open label arm 2 | Other | Participants will be randomised to BA sequence of drugs B: Approximately 8 weeks of 25mg Chlortalidone A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg Receives: Drug: Amlodipine; Drug: Chlortalidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of Skin sodium
This is planned for all participants
Measured: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Concentration of Skin Potassium
This is planned for all participants
Measured: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Systolic blood pressure
This is planned for all participants
Measured: All study visits - every 4 weeks up to week 16 which will be the study completion week
Secondary outcomes (4)
MRI skin sodium concentration
This is planned for all participants
Measured: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Concentration of Skin glycosaminoglycans
This is planned for all participants
Measured: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Diastolic blood pressure
This is planned for all participants
Measured: All study visits - every 4 weeks up to week 16 which will be the study completion week
Body weight
This is planned for all participants
Measured: Body weight measurement will be performed at baseline only.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2023
- Study startAug 2023 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London
- Responsible party
- Principal investigator, Dr Ian B Wilkinson, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Ian Wilkinson, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05976438
- Sponsor's protocol ID
- A096461
- Acronym
- INTREPID
- Status last verified
- Jul 2023
- First submitted
- 17 Jul 2023
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Relevance of Skin Sodium and Salt Sensitivity of Blood Pressure in Determining the Response to Anti-Hypertensive Drugs (INTREPID)
- ClinicalTrials.gov ID
- NCT05976438
- Acronym / sponsor ID
- INTREPID / A096461
- Conditions
- Hypertension
- Keywords
- Skin Sodium, Salt Sensitivity, Blood Pressure, Heart Disease, Cardiovascular
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- King's College London
- Study start
- Aug 2023 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 4 Aug 2023 (actual)
- 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.
Eating too much salt raises blood pressure and the risk of having a heart attack or stroke. The investigators do not fully understand why salt raises blood pressure, but storage of sodium in the body, particularly in the skin, may be important. For this reason, the investigators wish to study the link between skin sodium, blood pressure and cardiovascular risk in patients with high blood pressure, of different ethnicities, using techniques such as skin biopsy and magnetic resonance imaging (MRI). The results will provide detailed information on skin sodium storage and help us better understand the effects of blood pressure medications on these mechanisms. Ultimately, the investigators aim to develop personalized treatment guidelines for clinical use.
Detailed description
The physiological basis of salt sensitivity of blood pressure (SSBP) is poorly understood, and determining which patients have SSBP is not straightforward. Furthermore, determining salt sensitivity requires direct intervention tracking changes in blood pressure after salt challenge or depletion over several days. This makes identifying salt-sensitive individuals impractical in a clinical setting, hindering its application. It is crucial that the investigators elucidate the underlying mechanisms of salt-sensitivity, and through this understanding develop a biomarker of SSBP for clinical use.
From a review of recent studies it appears that in the short-term, accumulation of skin sodium during high salt intake attenuates the blood pressure response, while in the long-term, high skin sodium levels indicate a tendency for SSBP, hypertension and elevated cardiovascular risk. The reasons for this are not clear and merit further investigation. By refining methods for quantification of skin sodium and expanding its use in hypertension research, the clinicians can improve patient assessment, treatment prescription, and disease monitoring.
Using skin biopsy and sodium MRI provides a unique opportunity to study skin sodium handling and SSBP during antihypertensive treatment, and can provide insights into why hypertensives and certain ethnic groups have a higher incidence of SSBP. Sodium MRI may also help increase our understanding of the mechanisms by which diuretics work, both systemically and in the kidney and provide a way to identify salt-sensitive individuals for targeted clinical intervention.
Hypotheses:
- Skin sodium decreases with salt-dependent (diuretic) treatments but not salt-independent (calcium channel blocker) treatments.
- Diuretic-induced reductions in skin sodium correlate with reductions in blood pressure.
- Skin sodium is higher in populations traditionally known to be more salt sensitive, such hypertensive patients of black ethnicity.
Patients will be enrolled on to a randomised, open-label, two-treatment two-period crossover treatment. The hypertensive medication used in this study are Amlodipine 5 or 10mg and Chlortalidone 25mg.
The duration for individual participants will be approximately 16 weeks. Participants will have a total of 7 visits including screening/enrolment (visit 1) and baseline visit (visit 2).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open label arm 1 | Other | Drug: Amlodipine, Drug: ChlortalidoneParticipants will be randomised to AB sequence of drugs A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg B: Approximately 8 weeks of 25mg Chlortalidone |
| Open label arm 2 | Other | Drug: Amlodipine, Drug: ChlortalidoneParticipants will be randomised to BA sequence of drugs B: Approximately 8 weeks of 25mg Chlortalidone A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have given written informed consent to participate
- Aged 18 or above
- Be hypertensive defined as:
- OR
Key exclusion criteria (10 listed)
- Uncontrolled blood pressure ≥ 180/110mmHg
- Known or suspected secondary hypertension
- Pregnant or breastfeeding women
- Significant sensitivity or contraindications to any of the study medications
- Participants taking lithium or are regularly consuming non-steroidal anti-inflammatory drugs at variable doses
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 |
|---|---|---|
| AmlodipineAmlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive. | Drug | Open label arm 1, Open label arm 2 |
| ChlortalidoneChlortalidone 25mg will be one of the study drugs the patients will receive. | Drug | Open label arm 1, Open label arm 2 |
Primary outcome
Concentration of Skin sodium
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
This is planned for all participants
Concentration of Skin Potassium
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
This is planned for all participants
Systolic blood pressure
Time frame: All study visits - every 4 weeks up to week 16 which will be the study completion week
This is planned for all participants
4 secondary outcomes
MRI skin sodium concentration
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Concentration of Skin glycosaminoglycans
Time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
Diastolic blood pressure
Time frame: All study visits - every 4 weeks up to week 16 which will be the study completion week
Body weight
Time frame: Body weight measurement will be performed at baseline only.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
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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 Wilkinson principal investigator
Cambridge University Hospitals NHS Foundation Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Amlodipine and Chlortalidone in people with Hypertension, run by Cambridge University Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
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 6 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: status not confirmed, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Irene Sambath (01223 256621, irene.sambath@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of Skin sodium (time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Aug 2023.