Orthostatic Hypotension
Conditions
Keywords
Orthostatic Hypotension, Sodium, Diet
Brief summary
Background Orthostatic hypotension (OH) is a common cause of falls, and key source of morbidity and mortality due to injury (e.g. hip fracture). Current guidelines recommend increasing salt intake in patients with symptomatic orthostatic hypotension. However, the evidence underpinning this recommendation is poor, based primarily on small trials with very short-term follow-up (\< 6 weeks). Clinical Equipoise (Overall) High salt intake might improve quality of life and reduce the risk of falls, but might also increase the risk of cardiovascular disease, in patients with OH. Specific Objective of Current Application (Aim) To determine feasibility (recruitment, retention and adherence) of conducting a randomized controlled trial evaluating high salt intake in older adults with symptomatic orthostatic hypotension. To determine preliminary estimates of the effect of high salt intake on disease-specific quality of life, orthostatic blood pressure (BP) parameters, and cardiac blood biomarkers. Design: Phase IIa, parallel, double-blind, randomised controlled, single centre clinical trial of 12 month follow-up duration. Population: Older adults (≥65 years of age) with an objective diagnosis of symptomatic orthostatic hypotension Intervention: The intervention will be 5g/day of salt supplementation in the form of encapsulated sodium chloride. Outcome measures: Primary outcome (Feasibility) recruitment and retention rates, adherence with intervention and study protocol, completeness of follow-up. Secondary Outcome (Efficacy): i) clinical: change in Orthostatic Hypotension Questionnaire score, modification/addition of OH pharmacotherapy, and falls events, ii) physiological measures of orthostasis: change in difference between supine and nadir systolic BP, standing BP at 1 minute, 24 hour mean BP measured by 24 hour ambulatory BP monitor, iii) cardiovascular biomarkers. Clinical Importance: A recommendation for long-term increases in salt intake may have adverse cardiovascular consequences, which necessitates the identification of the optimal range of salt intake associated with greatest reduction in falls risk and lowest cardiovascular risk. Our study will provide preliminary evidence of treatment effect and assess feasibility, to inform a definitive trial.
Interventions
DIETARY_SUPPLEMENTSalt supplementation (encapsulated sodium chloride)
A high salt intake range will be achieved through unchanged dietary intake and supplementary salt in the form of 1.25g sodium chloride capsules at a dose of 5g/day in two divided doses
Sponsors
University of Galway
Health Research Board, Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study is open-label. Blinding of participants is not possible for practical reasons. However, there is blinded assessment of change in formula derived 24-hour urinary sodium, cardiovascular biomarkers and mean 24-hour ambulatory blood pressure.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥ 65 years of age * Documented history of orthostatic hypotension, defined by decrease in systolic blood pressure (SBP) of ≥20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥10 mmHg within three minutes of standing when compared with blood pressure from the supine position, or at head-up tilt testing. * A documented history of symptoms consistent with orthostatic hypotension including one of the following: light-headedness, dizziness, feeling faint, feeling like they may black out * Baseline salt intake expected to be in the moderate range (5-10g/day) based on screening questions * Willingness to supplement sodium intake * Ability to provide written informed consent
Exclusion criteria
* Severe supine hypertension (Systolic blood pressure≥180mmHg or diastolic blood pressure \>110mmHg) measured as average of three office readings * A diagnosis of Heart Failure (New York Heart Association (NYHA) Class III or IV symptoms or known left ventricular ejection fraction 30%, if more than one echo eligibility is defined by most recent echo) * CKD (eGFR \<30ml/min/1.73m2) based on eGFR measured within the last 6 months * Participants taking loop diuretics * Serum sodium \<125mmol at last measurement * Acute intercurrent illness * Prescribed high-salt diet (for clinical indication other than for OH) or low-salt diet for evidence based clinical indication * Participant unlikely to comply with study procedures or follow-up visits due to severe comorbid illness or other factor (e.g. inability to travel for follow-up visits) in opinion of research team * Inability to provide informed consent in the opinion of the investigator (for example due to severe cognitive impairment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment to target (primary feasibility outcome) | 15 months | Recruitment of 48 participants |
| Change in orthostatic hypotension questionnaire score (primary efficacy outcome) | 6 months | Change in symptoms and quality of life measured using disease specific questionnaire; Orthostatic Hypotension Questionnaire (OHQ) from baseline to final follow-up. All questionnaire items are scored 0 through 10 (higher scores = worse). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in individual components of OHQ from baseline to final follow-up | 6 months | Change in individual components of OHQ from baseline to final follow-up. All questionnaire items are scored 0 through 10 (higher scores = worse). |
| Rates of modification/addition of OH pharmacotherapy | 6 months | Rates of modification/addition of OH pharmacotherapy |
| Rates of modification/addition of anti-hypertensive therapy | 6 months | Rates of modification/addition of anti-hypertensive therapy |
| Falls events | 6 months | Number of falls events |
| Change in difference between supine and nadir blood pressure from baseline to final in-person follow-up | 6 months | Change in difference between supine and nadir blood pressure from baseline to final in-person follow-up |
| Change in standing BP at one minute and three minutes | 6 months | Change in standing BP at one minute and three minutes measured at active stand |
| Change in mean BP measured by 24 hour ambulatory BP monitor | 6 months | Change in mean BP measured by 24 hour ambulatory BP monitor |
| Change in cardiovascular biomarkers; proBNP and troponin | 6 months | Change in cardiovascular biomarkers; proBNP and troponin |
| Change in formula derived 24 hour urinary sodium from baseline to final in-person follow-up visit. | 6 months | Change in formula derived 24 hour urinary sodium |
| Change in renin-aldosterone ratio from baseline to final in-person follow-up visit. | 6 months | Change in renin-aldosterone ratio from baseline to final in-person follow-up visit. |
Countries
Ireland
Contacts
PRINCIPAL_INVESTIGATORMartin O'Donnell
University of Galway
PRINCIPAL_INVESTIGATORCatriona Reddin
University of Galway
PRINCIPAL_INVESTIGATORAndrew Smyth
University of Galway
Outcome results
None listed