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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

About this trial

This is an interventional basic science trial for Type2 Diabetes

Eligibility Criteria

35 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

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

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Effects of Ketone Bodies on Cognition in Type 2 Diabetes

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