Condition category
Nervous System Diseases
Date applied
21/12/2018
Date assigned
31/12/2018
Last edited
11/01/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world, affecting up to 3 in 100 people aged over 65 years. PD is characterised by the death of neurons (nerve cells) that release the chemical messenger dopamine. The death of these neurons contributes to the classic motor (movement) symptoms of PD, which include slow movement and tremors (shaking). It is also increasingly appreciated that PD causes a wide variety of other types of symptoms, including sleep problems, loss of smell, depression, apathy, and cognitive dysfunctions (problems with memory and thinking).
There is no cure for PD, although there are a number of available treatments. A non-pharmacological (non-drug) therapy that has shown promise is the ketogenic diet. The ketogenic diet tricks the body into thinking it’s in a state of starvation so that it produces molecules called ketone bodies. Ketone bodies represent a highly efficient source of fuel for the brain and serve several signaling functions that may counteract the progression and treat the symptoms of PD. Encouragingly, research on PD mice has shown that ketone bodies prevent the death of PD-sensitive dopamine-releasing neurons and also that they reduce the symptoms of PD. Furthermore, human patients who were on a strict ketogenic diet for 28 days experienced substantial improvements in their PD symptoms.
Unfortunately, ketogenic diets come with two major drawbacks. Firstly, they are extremely restrictive and difficult to keep to. Secondly, most of the fuel energy measured in calories comes from fat and may increase cardiovascular (heart and circulation) disease risk. A research team at the University of Oxford has recently invented a ketone body dietary supplement (DeltaG) that may be able to provide the pros of ketones without the cons of ketogenic diets. Results in healthy people has already demonstrated that DeltaG is a tolerable and safe way to increase ketone body levels and favorably alter energy metabolism. The main aim of this study is to investigate whether DeltaG can be used to reduce the symptoms of PD.

Who can participate?
Patients with Hoehn and Yahr stage 1 or 2 Parkinson’s disease who are taking L-dopa, who are between the ages of 40 and 80, and who are fluent in English.

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 be randomly allocated to one of two groups. One group will receive a ketone ester drink (DeltaG) and the other will receive a placebo control (dummy) drink. Participants will be expected to drink their respective drinks four times every day for 1 month. During the trial, participants will undergo a series of motor, non-motor, and blood tests conducted at the John Radcliffe Hospital and in their own homes.

What are the potential benefits and risks of participating?
Participants will need to provide blood samples, wear a continuous activity monitor, and use a smartphone application. The risks are low. DeltaG has been proven to be safe in humans, but can gastrointestinal (stomach) upset in a small proportion of people because of its bitter taste. Participants may experience improvements in their motor symptoms, sleep, sense of smell, cognitive function, and even mood.

Where is the study run from?
The John Radcliffe Hospital, Oxford (UK)

When is the study starting and how long is it expected to run for?
October 2018 to January 2021

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)
parkinsons.discovery@nhs.net

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 Symptoms

Study information

Scientific title

Supplementation with a ketone ester drink to alleviate the symptoms of Parkinson’s disease

Acronym

N/A

Study hypothesis

Ingestion of a ketone ester supplement (DeltaG) will improve the symptoms of Parkinson's disease.

Ethics approval

Integrated Research Application System (IRAS) Project ID: 256914
I plan to submit for ethics approval as soon as I receive the eight-digit ISRCTN code that I need to submit an IRAS form.

Study design

Longitudinal single-blind randomized placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Parkinson's disease

Intervention

To ensure equal group sizes, participants will be block randomized to a ketone ester or placebo control group. Following a 2-week period during which baseline measurements will be taken (weeks -2 to 0), members of each group will be asked to ingest a drink containing either 25 ml of ketone ester (DeltaG) or an equal volume of a taste-matched control fluid four times daily for 1 month (weeks 0 to 4). Participants will also be followed for 2 weeks after the conclusion of the intervention to monitor for any lasting changes (weeks 4 to 6). Over the course of the entire 2-month period, participants will visit the study location on a fortnightly basis and undergo a series of non-invasive, minimally burdensome motor, nonmotor, and biological tests in order to monitor for changes in functional status and disease pathology. Participant compliance will also be assessed to inform future studies and to inform whether or not we will choose to extend the intervention period. Depending on the preliminary results and participants’ compliance, we may want to extend the intervention by a further 2 months to monitor for cumulative (or additional) positive effects of the ketone supplement.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

1. Overall symptom severity in the drug "off" state assessed using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) at weeks 0 and 4
2. Daily activity and gait assessed using a continuous activity monitor (Axivity AX3) worn on the lower back by participants for 7 days before (weeks -2 to -1) and during (weeks 2 to 3) the intervention
3. Motor skills assessed using a smartphone application once a day
4. Olfaction assessed using the Sniffin’ Sticks 16-odor identification test at weeks 0, 4, and 6
5. Selective attention assessed using the Stroop color-word test at weeks 0, 4, and 6
6. Cognitive function assessed using the the Montreal Cognitive Assessment (MoCA) at weeks 0, 4, and 6
7. Fatigue assessed using the Fatigue Severity Scale (FSS) survey over the phone once per week during a randomly-timed compliance call
8. Quality of life of participant assessed using the PDQ-39 questionnaire at weeks 0, 4, and 6
9. Quality of life of participant's carer assessed using the PDQ-Carer questionnaire at weeks 0, 4, and 6
10. Parkinson's disease-related sleep disorder assessed using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) at week 0.

Secondary outcome measures

1. Blood uric acid measured in a fasted state at weeks 0, 2, 4, and 6
2. Blood glucose measured in a fasted state at weeks 0, 2, 4, and 6
3. Blood fructosamine measured in a fasted state at weeks 0, 2, 4, and 6
4. Blood insulin measured in a fasted state at weeks 0, 2, 4, and 6
5. Blood lipids measured in a fasted state at weeks 0, 2, 4, and 6
6. Blood C-reactive protein (CRP) measured in a fasted state at weeks 0, 2, 4, and 6
7. Blood inflammatory cytokines measured in a fasted state at weeks 0, 2, 4, and 6
8. Compliance assessed by calling patients at random once per week to ask them when they last consumed the study drink and to request that they blindly (we will mask the monitor) measure their own blood ketone levels by fingerstick
9. Participant subjective comments on their experiences taking the drink assessed using a consumer-style questionnaire at week 4

Uric acid is a major circulating antioxidant that tends to be depleted in the blood of patients with Parkinson’s disease. Participants’ glucose, fructosamine, insulin, and lipids levels will afford insight into the quality of their carbohydrate metabolism and relative cardiovascular risk. This is relevant because diabetes and heart disease are also age-related diseases and often present as comorbidities alongside Parkinson’s disease. CRP and inflammatory cytokines are markers of systemic inflammation, a phenomenon characteristic of, and involved in the development of, many age-related diseases.

Overall trial start date

01/10/2018

Overall trial end date

01/01/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Diagnosis of Parkinson's disease
2. Taking L-dopa
3. Hoehn and Yahr stages 1-2
4. Fluent in English
5. Capable of giving informed consent
6. Aged 40-80

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

48 participants divided equally into two groups.

Participant exclusion criteria

1. Communication impairments
2. Any disorder that the Chief Investigator deems may bias the study results or put the participant at risk

Recruitment start date

02/02/2019

Recruitment end date

02/02/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

John Radcliffe Hospital
Headley Way, Headington
Oxford
OX3 9DU
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

http://tdeltas.com

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 generated during and/or analyzed during the current study 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

Editorial Notes

11/01/2019: Internal review.