Skin Sodium and Salt Sensitivity of Blood Pressure

NCT ID: NCT05976438

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-31
• Study Completion Date: 2024-12-31

Brief 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. 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:

1. Skin sodium decreases with salt-dependent (diuretic) treatments but not salt-independent (calcium channel blocker) treatments.

2. Diuretic-induced reductions in skin sodium correlate with reductions in blood pressure.

3. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Open label arm 1

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

Group Type: OTHER

Amlodipine

Intervention Type: DRUG

Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.

Chlortalidone

Intervention Type: DRUG

Chlortalidone 25mg will be one of the study drugs the patients will receive.

Open label arm 2

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

Group Type: OTHER

Amlodipine

Intervention Type: DRUG

Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.

Chlortalidone

Intervention Type: DRUG

Chlortalidone 25mg will be one of the study drugs the patients will receive.

Interventions

Amlodipine

Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.

Intervention Type: DRUG

Chlortalidone

Chlortalidone 25mg will be one of the study drugs the patients will receive.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Have given written informed consent to participate

2. Aged 18 or above

3. Be hypertensive defined as:

1. Currently untreated with an ABPM day time average blood pressure or average home blood pressure of ≥135 mmHg (systolic) or ≥85 mmHg (diastolic)

OR

2. 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.

Exclusion Criteria

1. Uncontrolled blood pressure ≥ 180/110mmHg

2. Known or suspected secondary hypertension

3. Pregnant or breastfeeding women

4. Significant sensitivity or contraindications to any of the study medications

5. Participants taking lithium or are regularly consuming non-steroidal anti-inflammatory drugs at variable doses

6. Requirement to take any of the study drugs continuously e.g. ACEi and heart failure

7. Any clinically significant hepatic impairment

8. Any clinically significant kidney impairment

9. Concurrent participation in another clinical trial or study using systemic vasoactive medications or medications known to interact with the study drugs

10. Patients who are deemed unsuitable by the investigator on clinical grounds e.g. an abnormal heart rhythm due to Atrial Fibrillation (AF)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King's College London

OTHER

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Dr Ian B Wilkinson

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ian Wilkinson

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospitals NHS Foundation Trust

Locations

Addenbrooke's Hospital

Cambridge, , United Kingdom

St Thomas' Hospital

London, , United Kingdom

Countries

United Kingdom

Central Contacts

Irene Sambath

Role: CONTACT

irene.sambath@nhs.net

01223 256621

Facility Contacts

Irene Sambath

Role: primary

cuh.intrepid@nhs.net

Luca Faconti

Role: primary

Other Identifiers

A096461

Identifier Type: -

Identifier Source: org_study_id