Ketone Monoester and Blood Pressure

NCT05794802 | Unknown DMC

• 1 other identifier: 2023-5051
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the effect of acute consumption of a ketone monoester supplement in healthy male adults. The main questions it aims to answer are:

• To determine if acute consumption of a ketone monoester supplement modulates diurnal (measured in lab) and nocturnal blood pressure (assessed by ambulatory blood pressure monitoring; ABPM) compared to a taste-matched placebo. The investigators hypothesize that a ketone monoester supplement will acutely decrease systolic and diastolic blood pressure compared to the placebo. The same results are expected for diurnal and nocturnal blood pressure.
• To determine if acute consumption of a ketone monoester supplement improves glucose control measured with continuous glucose monitoring (CGM) following a standardized meal consumed 90 minutes after ingestion of the ketone supplement. The investigators hypothesize that a ketone monoester supplement, consumed 90 minutes before a meal, will decrease the 2-hour postprandial glucose incremental area under the curve (iAUC) and peak glucose compared to a placebo.
• To assess IL-10's ability to inhibit proinflammatory cytokine production (TNF- α and IL-1β) in LPS-stimulated whole blood cultures following the ingestion of β-OHB and placebo. The investigators hypothesize that β-OHB will augment the ability of IL-10 to inhibit TNF-α and IL-1β production compared to placebo. Using a double-blind placebo-controlled randomized crossover study design, 15 adults will participate in two experimental conditions. Participants will be recruited using a local recruitment database (Nabû), during presentations in community organizations, with posters at the University of Sherbrooke, and from word of mouth. Following screening, eligible participants will be invited for one baseline and two experimental conditions at the Research Centre on Aging (CdRV). During the baseline visit, the following assessments and tests will be conducted:
• resting heart rate (HR) and blood pressure;
• anthropometry and body composition;
• medical history and questionnaires on physical activity levels, dietary habits and anxiety symptoms;
• explanation of the dietary and physical activity logs;
• installation of accelerometers to control physical activity levels and sedentary behaviors over 10 days and CGM to assess glucose control over the subsequent 10 consecutive days. During the week following the baseline condition, participants will be invited to the laboratory for their first experimental condition (duration = 240 minutes). Participants will come to the lab in a fasted state (at least 12-hour overnight) to the lab at 8:00 am where following assessments and tests will be conducted:
• resting heart rate (HR) and blood pressure;
• ketone supplement or placebo consumption;
• blood samples and cold pressor test;
• standardized breakfast;
• galvanic skin response;
• visual analog scales assessing gastrointestinal discomfort, hunger and fullness;
• installation of ABPM and explanation of the dietary and physical activity logs. Forty-eight hours later, participants will complete the same experimental condition with the alternate supplement (ketone or placebo) according to their randomization.

Conditions

Blood Pressure

Keywords

ketone monoester; blood pressure; glucose homeostasis; heatlhy adults

Outcome Measures

Primary Outcomes (2)

• Change in blood pressure and ambulatory blood pressure

  Resting systolic and diastolic blood pressure (BP) will be measured after 5 minuntes of rest, in a sitting position using an automatic BP monitor (Spot Vital Signs LXi, Welch Allyn Inc., NY, USA). Three BP measurements will be taken interspersed with 1 minute between measurements. If a variation greater than 5 mmHg for BP is observed, a maximum of two more measurements will be taken. During the condition, blood pressure will be measured every 20 minutes. Ambulatory blood pressure will be performed over 24 h using ambulatory blood pressure monitoring (ABPM, IEM PWA Mobil-o-graph; I.E.M. GmbH, Germany). The ABPM will be installed on the non-dominant arm and BP will be measured every 20 minutes after the condition (after 12:00 pm) and every 30 minutes during the night. The nocturnal period will be determined with the participant before every condition.

  Baseline, before supplements' ingestion, each 20 minutes post-dose and during the subsequent 24 hours

• Effect on glucose homeostasis

  During the first visit to the CdRV, a continuous glucose monitor (CGM, G6™ sensor, Dexcom Inc., San Diego, CA, USA) will be installed on the arm of the participant, which is to be worn for the subsequent 10 days. During this period, the CGM will collect the following data: blood glucose following ingestion of the ketone supplement (90 minutes), postprandial blood glucose (for 2h following the standardized meal), 24-hour blood glucose, time in range, time spent in hyperglycemia (\> 10 mmol/L), hypoglycemia (\< 3.8 mmol/L), and mean nighttime blood glucose. For glycemic variability, the following indices will be calculated with Macros in Excel (Easy GV; version 9.0): standard deviation (SD), CV%, and CONGA1 (continuous overall net glycemic action). The CGM will be removed 24 h after the last experimental condition. Raw data will be downloaded from the monitor and analyzed using the Clarity platform (Dexcom Inc., San Diego, CA).

  Baseline and during the next 10 days

Secondary Outcomes (2)

• Changes in IL-10 inflammatory profile

  10 minutes pre-dose and 60 minutes post-dose in each condition

• Changes in transcriptomic analyses of peripheral blood mononuclear cells

  10 minutes pre-dose and 60 minutes post-dose

Study Arms (2)

BHB supplement condition

EXPERIMENTAL

Dietary Supplement: BHB supplement

Placebo solution condition

PLACEBO COMPARATOR

Other: Placebo solution

Interventions

BHB supplement DIETARY_SUPPLEMENT

Oral consumption of 0.5 g/kg of a BHB supplement (KE4; Ketoneaid®, Falls Church, Virginia, USA)

BHB supplement condition

Placebo solution OTHER

80 to 120 ml of a placebo solution, depending on the participant's body weight, with the addition of stevia and bitter agent solution (Bitrex, Scotland, UK) as well as the same flavouring as the ketone supplement drink (provided by Ketoneaid)

Placebo solution condition

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male
• to 45 years old

You may not qualify if:

• Changes in any type of medication in the last 6 months
• Individuals taking beta-blocker
• Prior history of cardiovascular disease or stroke
• Individuals following a ketogenic diet, low-calorie diet, periodic fasting regimen or consuming ketogenic supplements
• Currently smoking
• Unable to read or communicate in french or english

Sponsors & Collaborators

• Université de Sherbrooke: lead
• University of British Columbia: collaborator

Study Sites (1)

Centre de recherche sur le vieillissement

Sherbrooke, Quebec, J1H 4C4, Canada

Location

Study Officials

• Eléonor Riesco, PhD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eléonor Riesco, PhD

CONTACT

1-819-821-8000; e.riesco@usherbrooke.ca

Alexis Marcotte-Chénard, MSc

CONTACT

1-819-780-2220; alexis.marcotte-chenard@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: April 3, 2023
• Study Start: June 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)