Plain English Summary
Background and study aims
In both animals and humans, the infusion of acetoacetate or D-beta hydroxybutyrate (DβOHB) (also called ketone bodies) lowers blood glucose (sugar) levels. However, there is controversy on the mechanism of action behind this phenomenon and both insulin-dependent and -independent mechanisms have been proposed. This blood sugar lowering effect is greater in people with diabetes than in healthy adults and no mechanism behind this difference has been found. The aim of this study is to find out whether ketone bodies lower blood glucose by reducing the amount of available alanine for gluconeogenesis (generation of glucose).
Who can participate?
Healthy volunteers aged 18 - 70
What does the study involve?
Participants are asked to fast for 24 hours before their visit. During their visit they are asked to consume a mix of the ∆G ketone drink and water. Blood samples are collected over two hours to measure levels of glucose, BOHB, L-Alanine and L-Glutamine. The estimated volume of collected blood is less than 30 ml (or about one fl oz).
What are the possible benefits and risks of participating?
Finding the mechanism behind this phenomenon could lead to a useful new treatment for diabetes. There are no expected potential benefits for participants. Participants who complete the study will receive 50 GBP and refund of reasonable travel expenses. Inserting cannulas (tubes) for blood sampling can be uncomfortable but will always be performed by an experienced practitioner and local anaesthetic creams can be used in order to minimize any discomfort. There is a very small risk of infection, but to minimize this risk, the skin is cleaned thoroughly before the insertion. The tested dose of the ketone drink is among the lowest already studied. Doses three times greater than this have already proven to be safe. Participants receive advice on how to minimise the bad taste of the drink. In previous studies, the most reported side effects were mild nausea, abdominal distension and headache. Some participants might experience flushing which a is very well known and harmless effect of Vitamin B3 supplements and which typically resolves on its own in one or two hours. No risks or potential adverse effects are expected for the alanine supplementation groups as the dose matches the amount of alanine released by the muscle tissue in healthy adults.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
January 2018 to July 2018
Who is funding the study?
TdeltaS (UK)
Who is the main contact?
Dr Luis Adrian Soto Mota
adrian.soto@dpag.ox.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Dr Luis Adrian Soto Mota
ORCID ID
http://orcid.org/0000-0002-9173-7440
Contact details
Department of Physiology
Anatomy and Genetics.
Sherrington Building
Parks Road
Oxford
OX1 3PT
United Kingdom
+44 (0)1865 272 500
adrian.soto@dpag.ox.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
DELTAGMOA2018
Study information
Scientific title
The mechanism whereby an exogenous ketone drink lowers blood glucose
Acronym
Study hypothesis
Ketone bodies lower blood glucose by reducing the amount of available alanine for gluconeogenesis.
Ethics approval
East of England - Cambridge South Research Ethics Committee, 21/06/2018, 18/EE/0115
Study design
Single-centre interventional single-dose open-label study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Other
Trial type
Other
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Glucose and ketone bodies metabolism
Intervention
Ten healthy participants will be asked to fast for 24 hours before their visit. On their visit to the Department of Physiology and Genetics of the University of Oxford, they will be asked to consume a mix of 25 ml of the ∆G ketone drink and 25 ml of water. The trialists will perform 8-point curves of blood plasma Glucose, BOHB, L-Alanine and L-Glutamine over two hours. The estimated volume of collected blood is less than 30 ml (or approximately one fl oz).
Intervention type
Other
Phase
Drug names
Primary outcome measure
Blood glucose levels, measured using blood samples collected through a venous cannula at baseline and every 15 minutes during two hours
Secondary outcome measures
Blood alanine and fatty acid levels, measured using blood samples collected through a venous cannula at baseline and every 15 minutes during two hours
Overall trial start date
08/01/2018
Overall trial end date
31/07/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Participants must be fluent in English, have no communication impairments and should be willing and able to give informed consent for participation in the trial
2. Aged 18 – 70 (inclusive)
3. With no known medical diagnosis
4. Have had no course of medication, whether prescribed or over-the-counter, in the four weeks before the first trial dose and no individual doses in the final two weeks other than over the counter analgesics, vitamins and mineral supplements or, for females, oral contraceptives
5. Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner mechanical or pharmacological contraception during the trial and for 3 months thereafter
6. In the Investigator’s opinion, is able and willing to comply with all trial requirements
7. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial
Participant type
Healthy volunteer
Age group
Adult
Gender
Both
Target number of participants
10
Participant exclusion criteria
1. Female participant who is pregnant, lactating or planning pregnancy during the trial
2. Significant renal or hepatic impairment
3. Scheduled elective procedures requiring general anaesthesia during the trial
4. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial
5. Participants who have participated in another research trial involving an investigational product in the past 12 weeks
Recruitment start date
30/06/2018
Recruitment end date
03/07/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Oxford
Department of Physiology, Anatomy and Genetics
Parks Road
Sherrington Building
Oxford
OX1 3PT
United Kingdom
Sponsor information
Organisation
TdeltaS Ltd
Sponsor details
30 Upper High Street
Thame
OX9 3EZ
United Kingdom
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
TdeltaS
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication of the study results in a high-impact peer-reviewed journal in August 2019. The study protocol and statistical analysis plan will be available on request from Dr Adrian Soto Mota (adrian.soto@dpag.ox.ac.uk).
IPD sharing statement
Access will be granted to authorised representatives from the Sponsor, host institution and the regulatory authorities to permit trial-related monitoring, audits and inspections. To request it, contact Professor Kieran Clarke (info@tdeltas.com).
Intention to publish date
01/08/2019
Participant level data
Available on request
Basic results (scientific)
Publication list