SalT Supplementation in Older Adults With Orthostatic Intolerance Disorders (STOOD)

SalT Supplementation in Older Adults With Orthostatic Intolerance Disorders (STOOD): a Phase IIa Randomised Controlled Trial of Sodium Supplementation in Those Consuming Moderate Salt Intake.

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.

Study Overview

• Status: Recruiting
• Conditions: Orthostatic Hypotension
• Intervention / Treatment: Dietary supplement: Salt supplementation (encapsulated sodium chloride)

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Catriona Reddin; Phone Number: 086-1438101; Email: catriona.reddin@universityofgalway.ie

Study Locations

• Ireland
  • Galway, Ireland
    • Recruiting
    • Clinical Research Facility Galway/Galway University Hospital
    • Contact: Catriona Reddin, MB BCh BAO, MSc; Phone Number: 0861438101; Email: catriona.reddin@universityofgalway.ie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Salt supplementation; Salt supplementation in the form of 1.25g sodium chloride capsules at a dose of 5g/day in two divided doses	Dietary supplement: Salt 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
No Intervention: Usual salt intake (no change in intake)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment to target (primary feasibility outcome)	Recruitment of 48 participants	15 months
Change in orthostatic hypotension questionnaire score (primary efficacy outcome)	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).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of modification/addition of OH pharmacotherapy	Rates of modification/addition of OH pharmacotherapy	6 months
Rates of modification/addition of anti-hypertensive therapy	Rates of modification/addition of anti-hypertensive therapy	6 months
Change in difference between supine and nadir blood pressure from baseline to final in-person follow-up	Change in difference between supine and nadir blood pressure from baseline to final in-person follow-up	6 months
Change in standing BP at one minute and three minutes	Change in standing BP at one minute and three minutes measured at active stand	6 months
Change in mean BP measured by 24 hour ambulatory BP monitor	Change in mean BP measured by 24 hour ambulatory BP monitor	6 months
Change in cardiovascular biomarkers; proBNP and troponin	Change in cardiovascular biomarkers; proBNP and troponin	6 months
Change in formula derived 24 hour urinary sodium from baseline to final in-person follow-up visit.	Change in formula derived 24 hour urinary sodium	6 months
Change in renin-aldosterone ratio from baseline to final in-person follow-up visit.	Change in renin-aldosterone ratio from baseline to final in-person follow-up visit.	6 months
Change in individual components of OHQ from baseline to final follow-up	Change in individual components of OHQ from baseline to final follow-up. All questionnaire items are scored 0 through 10 (higher scores = worse).	6 months
Falls events	Number of falls events	6 months

Collaborators and Investigators

• Sponsor: University of Galway
• Collaborators: Health Research Board, Ireland
• Investigators: Principal Investigator: Martin O'Donnell, University of Galway; Principal Investigator: Catriona Reddin, University of Galway; Principal Investigator: Andrew Smyth, University of Galway

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 17, 2023
• First Submitted That Met QC Criteria: December 17, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Diet; Sodium; Orthostatic Hypotension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Hypotension, Orthostatic; Orthostatic Intolerance
• Other Study ID Numbers: C.A.3086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No