β-hydroxybutyrate, Glucose Metabolism and Prediabetes (CETUS)

Cross-over, Placebo-controlled, Randomized Trial of β-hydroxybutyrate in Prediabetes

The study aims to investigate changes in blood glucose metabolism after administration of a ketone ester drink.

Study Overview

• Status: Completed
• Conditions: PreDiabetes
• Intervention / Treatment: Other: HVMN Ketone; Other: Placebo

Detailed Description

New-onset prediabetes is the most significant risk factor for diabetes. Clinical studies in healthy human volunteers have demonstrated that ketone esters lower blood glucose levels in both fasting and fed state.

Participants will visit the COSMOS clinic on two occasions and will be randomly allocated to receive either the HVMN ketone drink or placebo, in a cross-over design. Blood samples will be collected sequentially every 30 minutes for up to 150 minutes. Blood samples will be assayed for glucose and other markers of glucose metabolism.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • University of Auckland; Auckland City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals over 18 years
• Individuals diagnosed with prediabetes; defined based on the American Diabetes Association guidelines
• History of at least one episode of acute pancreatitis
• Written informed consent

Exclusion Criteria:

• Individuals who are on a ketogenic diet or consuming nutritional ketone supplements
• History of cancer or chronic pancreatitis
• History of bariatric or gastrointestinal surgery
• Pregnant or breastfeeding women
• Individuals involved in intensive endurance training or competitive athletics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HVMN ketone drink; HVMN ketone drink will be given in a total volume of 100 ml.	Other: HVMN Ketone; Water-based, flavoured sport beverage
Placebo Comparator: Placebo; Placebo will be given in a total volume of 100 ml.	Other: Placebo; Water, stevia, malic acid, and thickening agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in plasma glucose concentration	Changes in plasma glucose concentration before and after administration of the intervention/placebo	Baseline, 30, 60, 90, 120, and 150 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in plasma insulin and C-peptide concentrations	Changes in plasma insulin and C-peptide concentrations before and after administration of the intervention/placebo	Baseline, 30, 60, 90, 120, and 150 minutes
Rate of change in plasma concentration of gut and pancreatic hormones	Changes in plasma concentrations of ghrelin, incretins, cholecystokinin, gastrin-releasing peptide, peptide YY, oxyntomodulin, motilin, glucagon, amylin, pancreatic polypeptide, and vasoactive intestinal peptide before and after administration of the intervention/placebo	Baseline, 30, 60, 90, 120, and 150 minutes
Rate of change in lipid profile and digestive enzymes	Changes in plasma concentration of triglycerides, glycerol, cholesterol, lipases before and after administration of the intervention/placebo	Baseline, 30, 60, 90, 120, and 150 minutes
Rate of change in plasma concentration of pro-inflammatory cytokines	Changes in plasma concentration of interleukin-1β, interleukin-6, leptin, tumor necrosis factor α, and monocyte chemoattractant protein-1 and other cytokines before and after administration of the intervention/placebo	Baseline, 30, 60, 90, 120, and 150 minutes
Rate of change in plasma concentration of markers of iron metabolism	Changes in plasma concentration of ferritin, hepcidin, transferrin receptor before and after administration of the intervention/placebo	Baseline, 30, 60, 90, 120, and 150 minutes
Correlation with body fat phenotypes	Differences in the association between rate of change in plasma glucose concentration and magnetic resonance imaging-derived visceral fat volume in the intervention/placebo	150 minutes
Correlation with body fat phenotypes	Differences in the association between rate of change in plasma glucose concentration and magnetic resonance imaging-derived subcutaneous fat volume in the intervention/placebo	150 minutes
Correlation with body fat phenotypes	Differences in the association between rate of change in plasma glucose concentration and magnetic resonance imaging-derived liver fat per centage in the intervention/placebo	150 minutes
Correlation with physical activity	Differences in the association between rate of change in plasma glucose concentration and metabolic equivalents score in the intervention/placebo	150 minutes

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand

Publications and helpful links

General Publications

• Liu Y, Bharmal SH, Kimita W, Petrov MS. Effect of acute ketosis on lipid profile in prediabetes: findings from a cross-over randomized controlled trial. Cardiovasc Diabetol. 2022 Jul 23;21(1):138. doi: 10.1186/s12933-022-01571-z.
• Bharmal SH, Alarcon Ramos GC, Ko J, Petrov MS. Abdominal fat distribution modulates the metabolic effects of exogenous ketones in individuals with new-onset prediabetes after acute pancreatitis: Results from a randomized placebo-controlled trial. Clin Nutr ESPEN. 2021 Jun;43:117-129. doi: 10.1016/j.clnesp.2021.03.013. Epub 2021 Mar 21.
• Bharmal SH, Cho J, Alarcon Ramos GC, Ko J, Cameron-Smith D, Petrov MS. Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial. J Nutr. 2021 Apr 8;151(4):921-929. doi: 10.1093/jn/nxaa417.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): August 16, 2019
• Study Completion (Actual): August 30, 2019

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Prediabetes; Ketones
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: 18/NTB/161

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
• product manufactured in and exported from the U.S.: Yes