Plain English Summary
Background and study aims
Parkinson’s disease (PD) is the world’s most common brain disease that affects motor function. The four main symptoms of PD are shaking, rigidness, problems with posture, and slowness of movement. These symptoms tend to get worse over time and are likely to affect all patients at some point during the disease process.
Research has focused on exercise as a way to slow, and even improve, the symptoms associated with PD. However, the effectiveness of exercise is limited by the fact the PD impairs a person’s ability to move and do exercise. Any therapeutic that could, even temporarily, improve physical ability could help to establish a positive loop where increased exercise capacity leads to improvement of the disease symptoms, which then improves physical functioning, and so on.
The Clarke research team at the University of Oxford has invented a ketone body dietary supplement (DeltaG) that may be able to stimulate such a positive loop. Results suggest that DeltaG alters energy metabolism and significantly increases exercise performance in human athletes. In this study, we want to investigate whether the performance-enhancing effects in athletes translate into persons struggling with PD.
Who can participate?
Patients with Hoehn and Yahr stage 1 or 2 Parkinson’s disease who are between the ages of 40 and 80 years, who are fluent in English, and who have no history of heart disease.
What does this study involve?
Participants will be recruited by word of mouth, emails to departmental mailing lists, posters located in university departments, and an advertisement on the Oxford Parkinson’s Disease Centre’s webpage. Potential participants will be interviewed to determine eligibility and asked to give informed consent.
Participants accepted to the study will perform an exercise test on a fixed-power stationary bicycle in which they begin cycling for 5 minutes at 100 Watts, after which the power requirement will increase by 25 Watts every 3 minutes until the participant stops pedaling voluntarily from exhaustion. Participants will perform the test 30 minutes after consuming either 350 mg/kg of ketone ester drink (DeltaG) or a control drink. Each participant will perform the test twice, once after consuming the DeltaG and once after consuming the control drink. The two tests will be separated by one week.
During the exercise test, participants will be asked to wear a face mask and heart rate monitor so that we can assess heart and lung function. Finally, participants will be asked to provide blood samples to investigate how the ketone ester and exercise affect metabolic processes.
What are the potential benefits and risks of participating?
There are not expected to be direct benefits for participants, although the results of the research could inform treatment options for patients with Parkinson’s disease. The risks to participants are minimal. The ketone supplement (DeltaG) might cause diarrhea, abdominal distension, and nausea. However, these gastrointestinal side effects are both rare and mild. DeltaG has 'Generally Regarded As Safe' (GRAS) certification from the US FDA and is commercially available in the United States as a sports supplement. Research has shown that repeated consumption of DeltaG at much higher doses is safe and generally well-tolerated.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
October 2018 to January 2020.
Who is funding the study?
TdeltaS Ltd., a spin out company from the University of Oxford.
Who is the main contact?
1. Mr. Nicholas Norwitz (DPhil student)
nicholas.norwitz@dpag.ox.ac.uk
2. Prof. Michele Hu (Chief Investigator)
michele.hu@ndcn.ox.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Mr Nicholas Norwitz
ORCID ID
http://orcid.org/0000-0002-0826-9069
Contact details
Sherrington Building
Sherrington Rd
Oxford
OX1 3PT
United Kingdom
+44 (0) 7444 054375
nicholas.norwitz@dpag.ox.ac.uk
Type
Scientific
Additional contact
Prof Michele Hu
ORCID ID
http://orcid.org/0000-0001-6382-5841
Contact details
Department of Neurology
West Wing
Level 3
John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom
Type
Public
Additional contact
Mr Nicholas Norwitz
ORCID ID
http://orcid.org/0000-0002-0826-9069
Contact details
Sherrington Building
Sherrington Rd
Oxford
OX1 3PT
United Kingdom
+44 (0) 7444 054375
nicholas.norwitz@dpag.ox.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
DeltaG PD Exercise, IRAS 257795
Study information
Scientific title
Supplementation with a ketone ester drink to improve exercise performance in patients with Parkinson's disease as measured by a cycle ergometer ramp test
Acronym
N/A
Study hypothesis
Ingestion of a ketone ester supplement (DeltaG) will improve exercise performance in patients with Parkinson’s disease. Therefore, we will report the DeltaG versus control differences on the following parameters: patients’ times to exhaustion, maximum work outputs, and cardiopulmonary test measures. We will also report on the effects of DeltaG and exercise on the levels of circulating metabolites.
Ethics approval
Approved (23/07/2019), NHS Health Research Authority (Skipton House, 80 London Road, London, SE1 6LH, UK; +44 (0)20 7972 2545; hra.approval@nhs.net), ref: 19/SC/0032.
Study design
Cross-over single-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
See additional files
Condition
Parkinson’s disease
Intervention
In this cross-over placebo-controlled trial, participants (n=15) will perform an exercise test on a fixed-power cycle ergometer in which they begin cycling for 5 minutes at 100 Watts, after which the power requirement increases by 25 Watts every 3 minutes until the participant stops pedaling voluntarily from exhaustion. Participants will be asked to come in before breakfast after an overnight fast and perform the test 30 minutes after consuming either a ketone drink or a taste-matched isocaloric control drink. The ketone drink will contain 25 g of ketone ester (DeltaG) and 45 g of dextrose and the control drink will contain 30 g of dextrose, 30 g of fructose, 15 g of maltodextrin, and 1.5 ml Symrise bitter flavor; product code: SY648352. Each participant will perform the test twice, once after consuming the ketone drink and once after consuming the control drink. The two tests will be separated by a one-week washout period and will be ordered randomly based on the flip of a coin.
During the exercise, participants will be asked to wear a face mask and heart rate monitor so that cardiopulmonary function (objective measures of exercise capacity) can be assessed. Finally, participants will provide blood samples immediately before consuming the study drinks, immediately before exercise, and immediately after exercise to investigate how DeltaG, in combination with carbohydrates and exercise, affects circulating levels of glucose, lactate, free fatty acid, and the ketone body beta-hydroxybutyrate.
Intervention type
Supplement
Phase
Drug names
Primary outcome measure
1. Time to exhaustion (Te)
2. Maximum wattage achieved by participants (Wmax)
3. Maximum heart rate (HRmax) assessed by heart rate monitor worn during the test
4. Oxygen consumption (VO2max) assessed using a respiratory gas capture face mask worn during the test
5. Respiratory exchange ratio (RER) assessed using respiratory gas capture face mask worn during the test.
Secondary outcome measures
1. Blood glucose level
2. Blood lactate level
3. Blood free fatty acid level
4. Blood beta-hydroxybutyrate level
These will be measured using samples taken from a venous cannula inserted into one of the participants’ arms immediately before consuming the study drink, immediately before exercise (30 minutes after consuming the study drink), and immediately after exercise.
Overall trial start date
01/10/2018
Overall trial end date
21/01/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Diagnosis of Parkinson's disease
2. Hoehn and Yahr stages 1-2
3. Fluent in English
4. Capable of giving informed consent
5. Aged 40-80 years
Participant type
Patient
Age group
Mixed
Gender
Both
Target number of participants
15
Total final enrolment
16
Participant exclusion criteria
1. Communication impairments
2. History or indications of cardiovascular disease
3. Any other disorder that the Principal Investigator deems may bias the study results or put the participant at risk
Recruitment start date
01/01/2019
Recruitment end date
01/01/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Oxford Brookes University
Headington Campus
Oxford
OX3 0BP
United Kingdom
Sponsor information
Organisation
TdeltaS Ltd
Sponsor details
30 Upper High Street
Thame
OX9 3EZ
United Kingdom
+44 (0) 1865 282248
info@tdeltas.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
TDeltaS Ltd
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
At the end of the study, the results will be presented at regional, national, and international meetings and published in medical journals. All published results and information will be anonymized.
IPD sharing statement:
The demographic data and individual participants’ study results will be available upon request from Nicholas Norwitz (nicholas.norwitz@dpag.ox.ac.uk) after the study concludes and for 5 years. If participants formally consent to have their individual data shared at the commencement of the study, it may be shared with other research teams upon justifiable request and will remain anonymized by a study-specific identification number.
Intention to publish date
01/07/2021
Participant level data
Available on request
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN16599164_Protocol_V1.4_04Dec2018).pdf Uploaded 07/12/2018
- ISRCTN16599164_PIS_V1.4_04Dec2018.pdf Uploaded 07/12/2018
- ISRCTN16599164_PIS_V1.5_08Dec2018.pdf Uploaded 10/12/2018
- ISRCTN16599164_Protocol_V1.5_08Dec2018.pdf Uploaded 10/12/2018
- ISRCTN16599164_PIS_V1.7_24Feb19.pdf uploaded 10/08/2020
- ISRCTN16599164_PROTOCOL_v1.12_21May19.pdf uploaded 10/08/2020