Protein Supplementation in Thiazide-induced Hyponatremia

NCT02614807 | Withdrawn

• 1 other identifier: 201504516
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

High blood pressure is very common among elderly Canadians. Clinical trials show clear benefit from lowering blood pressure in hypertensive elderly patients. These trials also demonstrate safety for several classes of blood pressure lowering drugs including water pills. However, water pills (thiazide diuretics) used for treatment of hypertension, can cause low sodium (hyponatremia), a significant clinical problem mainly among elderly and very elderly. Causes are age related decrease in kidneys' ability to get rid of water and low salt coupled with high water intake. A standard approach to treatment is lacking since higher salt intake may worsen hypertension, and lower water and higher protein intake is difficult to understand and actually implement. 'Nepro' is a nutritional drink high in protein, and low in potassium and sodium. It is used frequently as a dietary supplement in patients with kidney disease specifically for low sodium and high protein content. The high protein content in Nepro can help the kidney get rid of excess water, and the low sodium and potassium content will make this a safe option to use. Hence investigators propose a proof-of-concept trial on an easy to understand and administer, and relatively affordable solution to this issue. It could be summarized in one sentence: "Will a bottle of Nepro a day keep thiazide-caused hyponatremia and the doctor away?"

Conditions

Hyponatremia; Hypertension; Blood Pressure

Keywords

Dietary Supplement

Outcome Measures

Primary Outcomes (1)

• Efficacy: Correction of Hyponatremia (Serum Sodium > 133 mmol/L or reduction of deficit by 50%)

  The cumulative proportion of participants whose serum sodium either normalizes (\>133 mmol/L) by 4 weeks or who exhibit a decrease in deficit by 50% compared to baseline level.

  4 weeks

Secondary Outcomes (3)

• Feasibility: recruitment (proportion of patients who are screened and eligible, and proportion eligible who consent)

  4 weeks

• Safety: Tolerability of intervention (proportion of patients who can tolerate the Nepro supplement)

  2 and 4 weeks

• Safety: Worsening of hyponatremia (proportion of patients with Sodium < 125 mmol/L at 2 or 4 weeks)

  2 and 4 weeks

Study Arms (1)

Intervention

EXPERIMENTAL

All recruited patients will receive a standard endorsement of lower fluid intake (\<1.5 Litres/day) by a hypertension nurse and physician and an additional treatment consisting of a bottle (237 ml) of Nepro (a low sodium, low potassium content protein supplement) a day (supply for 4 weeks will be provided).

Dietary Supplement: Nepro

Interventions

Nepro DIETARY_SUPPLEMENT

The intervention is a dietary protein supplement. In the elderly hypertensive patient (assuming body weight of 70 kg) with mild to moderate hyponatremia free water excess is around 2.5 L. One bottle of Nepro/day will generate about 120 mosm to be excreted via urine. Given limited and mostly fixed urinary dilution and concentration between 300 and 800 mosm/L in the elderly and very elderly, one bottle of Nepro a day will result in an extra 400 ml of urine for a net loss of 163 ml of free water. Thus over the period of 2 to 4 weeks the calculated free water excess should be completely eliminated.

Intervention

Eligibility Criteria

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

You may qualify if:

• Elderly (\>65 years old)
• with diagnosed hypertension (HTN) treated with thiazide (hydrochlorothiazide) or thiazide-like (chlorthalidone and indapamide) diuretic and
• mild to moderate hyponatremia (Plasma sodium concentration 125-133 mmol/L).

You may not qualify if:

• Pregnancy
• estimated glomerular filtration rate (eGFR) \<45 ml/min/1.75 m2,
• Other causes of hyponatremia (liver cirrhosis, uncontrolled hypothyroidism, adrenal insufficiency)
• unable to provide informed consent;
• patients with generalized volume overload who may require immediate changes in diuretic therapy (at the discretion of treating HTN specialist);
• patients taking drugs which may interfere with urinary sodium excretion (such as carbamazepine, loop diuretics, potassium sparing diuretics, mineralocorticoid and glucocorticosteroids, selective serotonin receptor inhibitors, tricyclic antidepressants, amiodarone, and lithium);
• patients with moderate to severe hyponatremia (Plasma sodium concentration \< 125 mmol/L) who may require immediate discontinuation of the thiazide diuretic .

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H7W9, Canada

Location

Related Publications (1)

• Ruzicka M, McCormick B, Magner P, Ramsay T, Edwards C, Bugeja A, Hiremath S. Thiazide diuretic-caused hyponatremia in the elderly hypertensive: will a bottle of Nepro a day keep hyponatremia and the doctor away? Study protocol for a proof-of-concept feasibility trial. Pilot Feasibility Stud. 2018 Apr 6;4:71. doi: 10.1186/s40814-018-0263-y. eCollection 2018.

  PMID: 29636984 BACKGROUND

MeSH Terms

Conditions

Hyponatremia; Hypertension

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Marcel Ruzicka, MD PhD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: November 25, 2015
• Study Start: June 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: September 10, 2018

Record last verified: 2018-09

Locations

CA (1)