Effects of Ketone Bodies on Cognition in Type 2 Diabetes (KETOCOGNITION)
Primary Purpose
Type2 Diabetes, Ketonemia, Cognitive Change
Status
Completed
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
Ketone infusion
Saline infusion
Sponsored by
About this trial
This is an interventional basic science trial for Type2 Diabetes
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- Department of Research in Endocrinology, Bispebjerg University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Hyperketonemia - Placebo
Placebo - Hyperketonemia
Arm Description
Participants are randomly assigned to initially receive ketone infusion and then saline infusion
Participants are randomly assigned to initially receive saline infusion and then ketone infusion
Outcomes
Primary Outcome Measures
Cognitive composite score (global score)
Secondary Outcome Measures
Symbol Digit Modalities Test (SDMT)
Full Information
NCT ID
NCT03657537
First Posted
August 20, 2018
Last Updated
February 19, 2019
Sponsor
Bispebjerg Hospital
Collaborators
Psychiatric Centre Rigshospitalet
1. Study Identification
Unique Protocol Identification Number
NCT03657537
Brief Title
Effects of Ketone Bodies on Cognition in Type 2 Diabetes
Acronym
KETOCOGNITION
Official Title
KETOCOGNITION - Effects of Ketone Bodies on Cognition in Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
September 17, 2018 (Actual)
Primary Completion Date
February 14, 2019 (Actual)
Study Completion Date
February 14, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bispebjerg Hospital
Collaborators
Psychiatric Centre Rigshospitalet
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes, Ketonemia, Cognitive Change
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hyperketonemia - Placebo
Arm Type
Experimental
Arm Description
Participants are randomly assigned to initially receive ketone infusion and then saline infusion
Arm Title
Placebo - Hyperketonemia
Arm Type
Experimental
Arm Description
Participants are randomly assigned to initially receive saline infusion and then ketone infusion
Intervention Type
Drug
Intervention Name(s)
Ketone infusion
Intervention Description
β-hydroxybutyrate is infused intravenously.
Intervention Type
Drug
Intervention Name(s)
Saline infusion
Intervention Description
saline is infused intravenously.
Primary Outcome Measure Information:
Title
Cognitive composite score (global score)
Time Frame
When glucose levels have been stabilized for 40 minutes
Secondary Outcome Measure Information:
Title
Symbol Digit Modalities Test (SDMT)
Time Frame
When glucose levels have been stabilized for 40 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
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.
Facility Information:
Facility Name
Department of Research in Endocrinology, Bispebjerg University Hospital
City
Copenhagen
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
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Effects of Ketone Bodies on Cognition in Type 2 Diabetes
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