Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT04556279 |
| Other study ID # |
20HH6283 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2021 |
| Est. completion date |
March 2022 |
Study information
| Verified date |
May 2024 |
| Source |
Imperial College London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This study looks at how hypertensive patients, with high levels of aldosterone
(hyperaldosteronism) differ from hypertensive patients without hyperaldosteronism with
regards to markers of salt appetite. It also looks at how salt appetite changes after
treatment of hyperaldosteronism. Salt makes food taste good and when our bodies need salt our
brains make us like salty food even more. A high salt diet contributes to hypertension and a
low salt diet is an important aspect of the treatment of hypertension. Unfortunately patients
find it difficult to adhere to a low salt diet. Aldosterone is produced by the adrenal
glands, its release is stimulated by a salt need and it has been shown, in rodent models, to
activate pathways in the brain which drive a salt appetite. Mice with enhanced activity of
the aldosterone pathway in the brain become hypertensive due to increased salt intake.
Hyperaldosteronism, in humans, results in hypertension. The contribution of salt appetite, as
opposed to the effect of aldosterone on the kidney's retention of salt and other systems, is
unknown. Human studies have shown that when a human has a salt appetite, the concentration at
which they can detect the taste of salt reduces, they increase their preference for salty
food, and they consume more salt.
When hyperaldosteronism is suspected in a hypertensive patient, they attend hospital for a
day of investigations. Patient who are shown to have hyperaldosteronism have subsequent
visits for imaging of their adrenals and sampling of blood from the adrenal vein to diagnose
aldosterone producing adenomas (small tumours) which may be removed surgically, if not
suitable for surgery, the hyperaldosteronism is treated with medication. This study will
recruit hyperaldosteronism patients to investigate the effect of aldosterone on salt appetite
by testing salt taste threshold, salt taste preference and intake before and after treatment.
Description:
Aims
1. To determine if hypertensive patients with primary hyperaldosteronism have a lower salt
taste threshold and heightened preference for salty soup compared to hypertensive
patients with secondary aldosterone levels and a healthy control reference group.
2. To determine if treating primary hyperaldosteronism, with removal of aldosterone
producing adrenal adenomas or medical blockade of aldosterone, results in changes in
salt taste threshold and preference for salty soup.
STUDY DESIGN
This will be a non-interventional observational study examining a cohort of adult
patients with hypertension under the care of Imperial College Healthcare NHS Trust who
are being investigated and treated for primary hyperaldosteronism. No clinical
intervention will occur as part of this study outside of their standard clinical
practice. The schedule of events for each study will occur within 6 months.
Visit 1 This coincides with the saline infusion test.
According to the outcomes of the adrenal MDT discussion subsequent visits will depend on
clinical plan (no further investigation or treatment, medical or surgical treatment) and
will coincide with:
Visit 2 i) adrenal venous sampling (to distinguish unilateral from bilateral disease).
ii) clinic follow up after introduction of mineralocorticoid receptor antagonist (for
patients deemed unsuitable for adrenal vein sampling)
Visit 3 i) surgical outpatient assessment for removal of an adrenal adenoma. ii) clinic
follow-up after introduction of mineralocorticoid receptor antagonists (for patients who
carry unacceptably high risks for adrenal surgery or do not wish to have surgery, or
deemed not suitable for removal of adrenal adenoma post adrenal vein sampling e.g. with
bilateral disease).
Visit 4 i) clinic follow up after adrenal adenoma removal.
The protocol of investigation for each visit will consist of the following (total time
~60 mins ):
Salt taste threshold testing This involves the participant, whilst blindfolded, tasting
saline solutions, of varying concentration. The solution is sprayed onto the
participant's tongue, the participant then states if the solution contains salt or not.
Up to 20 solutions are tested (~10 mins) (Ohla et al., 2017).
VAS and gLMS training Participants are trained to use labelled hedonic scales (LHS)
(Wood et al., 2009) and general linear model sales (gLMS) (Green et al., 1996) to rate
sensations using an established protocol (Veldhuizen et al., 2017) (5 mins) (Appendix
8).
Salt taste preference testing This involves swilling a solution (soup of variable salt
concentration) in the mouth then expectorating into a bowl. The subject then rates the
solution on various parameters, for example liking, how it relates to "just right"
saltiness, and intensity, using a gLMS. LHS or VAS. Each solution will be repeated 3
times. A sweet solution and bitter solution are also tested. This will take up to 40
mins.
Saliva collection Saliva will be collected by asking participants to spit into a tube
for up to 5 mins. Saliva will be analysed for electrolytes including sodium and
potassium .
Questionnaires i) Internal state questionnaire to assess internal state: hunger, thirst,
fullness, pleasantness to eat, stress, anxiety, sleepiness, volume able to eat, nausea
(5 mins) (Appendix 9).
ii) Positive and Negative Affect Schedule (PANAS) to measure positive and negative mood
(Watson et al., 1988).
iii) Derby Salt questionnaire (DSQ) to assess habitual salt intake. iv) Beck's
depression inventory (BDI) (visit 1 only) to screen for significant depression which is
a contraindication
3.3 Procedures
3.3.1 Visit 1 (Saline infusion test) Patient arrives at 8 am (i) Blood pressure, heart
rate, weight recorded on admission (standard care). (ii) Study explained, questions
answered and patient is consented (iii) Patient is cannulated and blood taken for plasma
aldosterone, plasma renin activity, U&Es (standard care).
(iv) Patient remains in the seated position for at least 30 mins before infusion begins
(standard care). During this time the taste tests are completed and saliva collected.
(v) 2 litres of 0.9% saline are infused over 4 hours, starting at 9.00 a.m. (standard
care). During this time the questionnaires will be completed.
(vi) Blood pressure, oxygen saturation and heart rate are monitored throughout the test
(standard care).
(vii) After 4 hours (i.e. 1 pm), further blood sample are taken for aldosterone, renal
function and electrolytes (standard care).
(viii) Patient discharged as per standard clinical care.
3.3.2 Visits 2-4 This will be dictated by clinical pathway according to outcome of the
adrenal MDT discussion.
3.3.2.1 Coincide with adrenal venous sampling. (i) Blood pressure, heart rate and weight
recorded, and patient is cannulated on admission and blood samples sent (standard care).
(ii) Confirmation is made that the patient is happy to continue with study. (v) Taste
tests undertaken on the ward whilst the patient is waiting to go to the interventional
radiology suite.
(vi) Questionnaires will be completed if sufficient time. (vii) Adrenal venous sampling
(standard clinical care) (viii) Post procedure observation period (standard clinical
care). Questionnaires and taste tests completed if needed.
(ix) Patient discharged after observation period (standard clinical care).
3.3.2.2 Coincide with outpatient surgical consultation for adrenalectomy (If not
convenient for the patient this may occur when the patient attends for pre-op assessment
clinic).
(i) Patient telephoned by the research team the week prior to appointment to remind the
participant that study visit will occur and that the patient remains well.
(ii) Patient attends clinic and has blood tests, observations and review by the surgical
team, (standard care).
(iii) Confirmation is made that the patient is happy to continue with study. (iv) Taste
tests done and questionnaires will be completed in an out-patients room or Imperial NIHR
Clinical Research Facility.
3.3.2.3 Coincide with out-patient clinic follow-up visit after introduction of
mineralocorticoid receptor antagonists or surgical removal of adrenal adenoma.
(i) Patient telephoned by the research team the week prior to clinic appointment to
remind the participant that study visit will occur and check that the patient remains
well.
(ii) Patient attends clinic and has blood tests, observations and review by
endocrinology team (standard care).
(iii) Taste tests done, saliva collected and questionnaires completed before or after
clinical review in out-patients (Hammersmith, Charing Cross, St. Mary's Hospitals) or
Imperial NIHR Clinical Research Facility, Hammersmith Hospital.
(iv) Patient thanked for taking part in the study (this is the last visit).
3.4 Saliva analysis and storage
Saliva will be stored in the laboratories of Dr Tony Goldstone, PsychoNeuroEndocrinology
Research Group. These are located in the, Commonwealth Building, Imperial College
London, Hammersmith Hospital. This area has restricted access to research staff only and
only research team members will have access to the stored samples. Following analysis
samples will be stored by the research team pending ethical approval for use in another
project.
