Type2 DiabetesPhase 1KETOCOGNITIONNCT03657537
Effects of Ketone Bodies on Cognition in Type 2 Diabetes
A Phase 1 study testing Ketone infusion and Saline infusion in people with Type2 Diabetes and Ketonemia, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
Diabetes negatively affects cognition and increases the risk of developing overt dementia. Decreased cerebral glucose metabolism may be contributing to this effect, thus providing a glucose substitute using ketone bodies might improve neuronal function. Read more about this study
- Who is it for?
- Ages 35 to 70 years
- Conditions the study is for
- Type2 Diabetes, Ketonemia, Cognitive Change
- What is being tested?
- Ketone infusion and Saline infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteDenmark
- Study dates
- 17 Sep 2018to 14 Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed and written consent
- Clinically diagnosed type 2 diabetes mellitus for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO)).
- Normal haemoglobin ≥ 8.0 mmol/L (male) or ≥ 6.4 mmol/L (female)
- Male or female participants aged 35-70 years, both inclusive.
- Treated with diet or any antidiabetic medication except insulin and SGLT2i within the last 3 weeks.
- HbA1c ≤ 9.5 % by local laboratory analysis.
- BMI > 23 kg/m2 and < 35 kg/m2
Who cannot join
- Receipt of any investigational medicinal product within 3 months prior to screening.
- Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder.
- Nephropathy (serum creatinine levels ≥ 126 μmol/L (male) or ≥ 111 μmol/L (female)).
- Cardiac problems defined as decompensated heart failure (New York Heart Association (NYHA) class III and IV) at any time and/or angina pectoris within the last 12 months and/or acute myocardial infarction at any time.
- Active or recent malignant disease.
- Treatment with drugs that cannot be paused for 12 hours.
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- Repeated resting blood pressure at screening outside the range 90-150 mmHg for systolic or 50-100 mmHg for diastolic. This exclusion criterion also pertains to subjects taking antihypertensives.
- Inability to perform cognitive tests as assessed by the investigators (e.g. visual or auditory impairment).
- Known abnormalities of the central nervous system or any endocrinological (with the exception of diabetes mellitus and euthyroid goiter), haematological, neurological, psychiatric diseases or other major disorders that in the opinion of the investigator precludes compliance with the protocol, evaluation of the results or represent an unacceptable risk for the participant's safety.
- Proliferative retinopathy (funduscopy performed within 12 months before the screening is acceptable) and/or severe neuropathy.
- Current treatment with systemic drugs, which may interfere with glucose metabolism.
- Significant history of alcoholism or drug/chemical abuse as per investigator's judgement.
- Current tobacco user (smoking or nicotinic product use 3 months prior to screening).
- Severe hypoglycaemic event during the past 6 months.
- Known hypoglycaemia unawareness.
- Participants with mental incapacity or language barriers precluding adequate understanding or co-operation or who, in the opinion of the investigator or their general practitioner, should not participate in the trial.
- For females only: Pregnancy, breast-feeding status or intention of becoming pregnant during the trial.
- Any chronic disorder or severe disease that in the opinion of the investigator might endanger participant's safety or compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Research in Endocrinology, Bispebjerg University Hospital
Copenhagen
About this study
Official title: KETOCOGNITION - Effects of Ketone Bodies on Cognition in Type 2 Diabetes
Diabetes negatively affects cognition and increases the risk of developing overt dementia. Decreased cerebral glucose metabolism may be contributing to this effect, thus providing a glucose substitute using ketone bodies might improve neuronal function.
In this study the investigators propose to provide quantitative results on cognitive performance during acute hyperketonemia in patients with type 2 diabetes.
Read the detailed description
It has been proposed that hypometabolism in the brain contributes to the neuropathology that leads to Alzheimer's disease (AD). Additionally cognitive disturbances in patients with AD are associated with and paralleled by a decrease in cerebral glucose metabolism. This AD-like reduction in cerebral metabolism has also been associated with insulin-resistance, and may contribute to one of the links between diabetes and AD. Therefore manipulating neuro-energetics by providing a glucose substitute seems to be a means of improving neuronal function.
Here the investigators will examine the effect of ketone bodies on cognitive performance in patients with type 2 diabetes by a randomized cross-over trial. Each subject will meet for two experimental visits separated by 2-6 weeks. During the two visit days subjects will, in a randomized order, receive ketone bodies (β-hydroxybutyrate) or placebo (saline) intravenously. On both test days plasma glucose levels will be clamped. After glucose levels have been stabilized cognitive performance will be assessed by a battery of validated cognitive tests.
- Conditions
- Type2 Diabetes, Ketonemia, Cognitive Change
- Being tested
- Ketone infusion, Saline infusion
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone infusionDrug
β-hydroxybutyrate is infused intravenously.
Saline infusionDrug
saline is infused intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Hyperketonemia - Placebo | Experimental | Participants are randomly assigned to initially receive ketone infusion and then saline infusion Receives: Drug: Ketone infusion; Drug: Saline infusion |
| Placebo - Hyperketonemia | Experimental | Participants are randomly assigned to initially receive saline infusion and then ketone infusion Receives: Drug: Ketone infusion; Drug: Saline infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive composite score (global score)
Measured: When glucose levels have been stabilized for 40 minutes
Secondary outcomes (1)
Symbol Digit Modalities Test (SDMT)
Measured: When glucose levels have been stabilized for 40 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2018
- Study start17 Sep 2018
- Primary completion14 Feb 2019
- Study completion14 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Psychiatric Centre Rigshospitalet
- Responsible party
- Principal investigator, Nicole Jacqueline Jensen, Bispebjerg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03657537
- Sponsor's protocol ID
- H-18010656
- Acronym
- KETOCOGNITION
- Status last verified
- Feb 2019
- First submitted
- 20 Aug 2018
- Last updated
- 20 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KETOCOGNITION - Effects of Ketone Bodies on Cognition in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03657537
- Acronym / sponsor ID
- KETOCOGNITION / H-18010656
- Conditions
- Type2 Diabetes, Ketonemia, Cognitive Change
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Collaborators
- Psychiatric Centre Rigshospitalet
- Study start
- 17 Sep 2018 (actual)
- Primary completion
- 14 Feb 2019 (actual)
- Study completion
- 14 Feb 2019 (actual)
- First posted
- 5 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diabetes negatively affects cognition and increases the risk of developing overt dementia. Decreased cerebral glucose metabolism may be contributing to this effect, thus providing a glucose substitute using ketone bodies might improve neuronal function.
In this study the investigators propose to provide quantitative results on cognitive performance during acute hyperketonemia in patients with type 2 diabetes.
Detailed description
It has been proposed that hypometabolism in the brain contributes to the neuropathology that leads to Alzheimer's disease (AD). Additionally cognitive disturbances in patients with AD are associated with and paralleled by a decrease in cerebral glucose metabolism. This AD-like reduction in cerebral metabolism has also been associated with insulin-resistance, and may contribute to one of the links between diabetes and AD. Therefore manipulating neuro-energetics by providing a glucose substitute seems to be a means of improving neuronal function.
Here the investigators will examine the effect of ketone bodies on cognitive performance in patients with type 2 diabetes by a randomized cross-over trial. Each subject will meet for two experimental visits separated by 2-6 weeks. During the two visit days subjects will, in a randomized order, receive ketone bodies (β-hydroxybutyrate) or placebo (saline) intravenously. On both test days plasma glucose levels will be clamped. After glucose levels have been stabilized cognitive performance will be assessed by a battery of validated cognitive tests.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hyperketonemia - Placebo | Experimental | Drug: Ketone infusion, Drug: Saline infusionParticipants are randomly assigned to initially receive ketone infusion and then saline infusion |
| Placebo - Hyperketonemia | Experimental | Drug: Ketone infusion, Drug: Saline infusionParticipants are randomly assigned to initially receive saline infusion and then ketone infusion |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Informed and written consent
- Clinically diagnosed type 2 diabetes mellitus for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO)).
- Normal haemoglobin ≥ 8.0 mmol/L (male) or ≥ 6.4 mmol/L (female)
- Male or female participants aged 35-70 years, both inclusive.
- Treated with diet or any antidiabetic medication except insulin and SGLT2i within the last 3 weeks.
Key exclusion criteria (18 listed)
- Receipt of any investigational medicinal product within 3 months prior to screening.
- Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder.
- Nephropathy (serum creatinine levels ≥ 126 μmol/L (male) or ≥ 111 μmol/L (female)).
- Cardiac problems defined as decompensated heart failure (New York Heart Association (NYHA) class III and IV) at any time and/or angina pectoris within the last 12 months and/or acute myocardial infarction at any time.
- Active or recent malignant disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketone infusionβ-hydroxybutyrate is infused intravenously. | Drug | Hyperketonemia - Placebo, Placebo - Hyperketonemia |
| Saline infusionsaline is infused intravenously. | Drug | Hyperketonemia - Placebo, Placebo - Hyperketonemia |
Primary outcome
Cognitive composite score (global score)
Time frame: When glucose levels have been stabilized for 40 minutes
1 secondary outcome
Symbol Digit Modalities Test (SDMT)
Time frame: When glucose levels have been stabilized for 40 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketone infusion and Saline infusion in people with Type2 Diabetes and Ketonemia, run by Bispebjerg Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive composite score (global score) (time frame: When glucose levels have been stabilized for 40 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2019.