Clinical trial NCT03889210: β-hydroxybutyrate, Glucose Metabolism and Prediabetes
Official title: Cross-over, Placebo-controlled, Randomized Trial of β-hydroxybutyrate in Prediabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: PreDiabetes
Keywords: Ketones
Prediabetes
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
First posted: 2019-03-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of change in plasma glucose concentration
timeFrame: Baseline, 30, 60, 90, 120, and 150 minutes
Secondary outcomes:
measure: Rate of change in plasma insulin and C-peptide concentrations
timeFrame: Baseline, 30, 60, 90, 120, and 150 minutes
measure: Rate of change in plasma concentration of gut and pancreatic hormones
timeFrame: Baseline, 30, 60, 90, 120, and 150 minutes
measure: Rate of change in lipid profile and digestive enzymes
timeFrame: Baseline, 30, 60, 90, 120, and 150 minutes
measure: Rate of change in plasma concentration of pro-inflammatory cytokines
timeFrame: Baseline, 30, 60, 90, 120, and 150 minutes
measure: Rate of change in plasma concentration of markers of iron metabolism
timeFrame: Baseline, 30, 60, 90, 120, and 150 minutes
measure: Correlation with body fat phenotypes
timeFrame: 150 minutes
measure: Correlation with body fat phenotypes
timeFrame: 150 minutes
measure: Correlation with body fat phenotypes
timeFrame: 150 minutes
measure: Correlation with physical activity
timeFrame: 150 minutes
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: University of Auckland; Auckland City Hospital
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.