Impact of NaHCO3- on Exercise Hyperpnea

Effect of Induced Metabolic Alkalosis by Sodium Bicarbonate Administration on the Ventilatory Response to Exercise in Healthy Adults

An abnormally high V̇E/V̇CO2 response to exercise is a key pathophysiological feature of patients with chronic cardiopulmonary disease that is associated with adverse health outcomes. It follows that any intervention capable of decreasing the V̇E/V̇CO2 response to exercise has the potential to improve clinical and/or patient-reported outcomes. The investigators of this trial will compare the effects of orally administered sodium chloride (4 g, placebo) and sodium bicarbonate (0.3 g/kg of body mass) on ventilation, breathing pattern, dynamic operating lung volume, gas exhange, cardiovascular, metabolic and symptom parameters during symptom-limited, high-intensity, constant-work-rate cycle exercise testing in healthy adults aged 20-40 years.

Study Overview

• Status: Completed
• Conditions: Pulmonary Ventilation
• Intervention / Treatment: Drug: Sodium Bicarbonate; Drug: Sodium Chloride

Detailed Description

The ventilatory response (V̇E) to exercise-induced increases in the rate of CO2 production (V̇CO2) depends on the regulated level of arterial PCO2 (PaCO2) and the dead space to tidal volume ratio (VD/VT).

An abnormally high V̇E/V̇CO2 response to exercise, reflecting a high VD/VT and/or low PaCO2 equilibrium point, is a key pathophysiological feature of patients with chronic cardiopulmonary disease, including heart failure, pulmonary arterial hypertension, interstitial lung disease and chronic obstructive pulmonary disease. In these patient groups, exercise ventilatory inefficiency is associated with: disease severity and progression; exercise intolerance; exertional breathlessness; and increased risk of hospitalization, major cardiac events and mortality. It follows that any intervention capable of decreasing the V̇E/V̇CO2 response to exercise has the potential to improve clinical and/or patient-reported outcomes. Unfortunately, our ability to enhance exercise ventilatory efficiency is limited by the fact that, with the possible exception of lung volume reduction surgery in chronic obstructive pulmonary disease and pulmonary vasodilator therapy in pulmonary arterial hypertension and heart failure, ventilation-perfusion abnormalities reflecting a high VD/VT are often irreversible.

A largely unexplored approach to decreasing the V̇E/V̇CO2 response to exercise is increasing the PaCO2 equilibrium point by inducing a metabolic alkalosis via administration of an alkalizing agent such as sodium bicarbonate (NaHCO3). Thus, the primary objective of this randomized, double blind, placebo controlled, crossover study was to test the hypothesis that increasing the PaCO2 equilibrium point via induced acute metabolic alkalosis by single-dose oral administration of NaHCO3 would decrease in the V̇E/V̇CO2 ratio at its lowest point ("nadir") during high-intensity constant-load cycle exercise testing in healthy adults.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S4
      • McGill University, Department of Kinesiology & Physical Education, Clinical Exercise & Respiratory Physiology Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy
• Non-smoking
• Habitually active
• Non-obese (Body Mass Index <30 kg/m2)
• Normal lung function on spirometry

Exclusion Criteria:

• Self-reported gastrointestinal, cardiovascular, vascular, respiratory, kidney, liver, musculoskeletal, endocrine, neuromuscular and/or metabolic disease/dysfunction
• Taking doctor prescribed medications other than oral contraceptives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sodium Bicarbonate; Ingestion of sodium bicarbonate (0.3 g/kg of body mass)	Drug: Sodium Bicarbonate
PLACEBO_COMPARATOR: Sodium Chloride; Ingestion of sodium chloride (4 g)	Drug: Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory equivalent to carbon dioxide (V̇E/V̇CO2) at its lowest point ("nadir") during exercise	The V̇E/V̇CO2 nadir will be identified as the lowest 30-sec average data point during constant-load cycle exercise testing	Participants will be followed until all study visits are complete, an expected average of 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial pressure of carbon dioxide in the arterialized capillary blood (PacCO2)	PacCO2 (mmHg) will be measured at rest 90-min post-dose	Time Frame: Participants will be followed until all study visits are complete, an expected average of 3 weeks

Collaborators and Investigators

• Sponsor: McGill University

Publications and helpful links

Helpful Links

• Clinical Exercise & Respiratory Physiology Laboratory (CERPL) of McGill University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2015
• Primary Completion (ACTUAL): April 1, 2016
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (ACTUAL): February 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 20, 2017
• Last Update Submitted That Met QC Criteria: February 15, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Exercise; Sodium Bicarbonate; Ventilatory equivalent for carbon dioxide
• Other Study ID Numbers: A02-M19-15B

Plan for Individual participant data (IPD)

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