SalT Supplementation in Older Adults With Orthostatic Intolerance Disorders

NCT06188663 | Recruiting Phase 2 DMC

• 1 other identifier: C.A.3086
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Orthostatic Hypotension

Keywords

Orthostatic Hypotension; Sodium; Diet

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Change in individual components of OHQ from baseline to final follow-up

  6 months

• Rates of modification/addition of OH pharmacotherapy

  6 months

• Rates of modification/addition of anti-hypertensive therapy

  6 months

• Falls events

  6 months

• Change in difference between supine and nadir blood pressure from baseline to final in-person follow-up

  6 months

Study Arms (2)

Salt supplementation

ACTIVE COMPARATOR

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)

Usual salt intake (no change in intake)

NO INTERVENTION

Usual salt intake (no change in intake)

Interventions

Salt supplementation (encapsulated sodium chloride) DIETARY_SUPPLEMENT

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

Salt supplementation

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Galway: lead
• Health Research Board, Ireland: collaborator

Study Sites (1)

Clinical Research Facility Galway/Galway University Hospital

Galway, Ireland

RECRUITING

MeSH Terms

Conditions

Hypotension, Orthostatic

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Martin O'Donnell

  University of Galway

  PRINCIPAL INVESTIGATOR

• Catriona Reddin

  University of Galway

  PRINCIPAL INVESTIGATOR

• Andrew Smyth

  University of Galway

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catriona Reddin

CONTACT

086-1438101; catriona.reddin@universityofgalway.ie

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Fellow, Geriatric Medicine SpR

Study Record Dates

• First Submitted: December 17, 2023
• First Posted: January 3, 2024
• Study Start: July 9, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)