Effects of Ketone Bodies on Cognition in Type 2 Diabetes

NCT03657537 | Completed Phase 1

• 1 other identifier: H-18010656
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes; Ketonemia; Cognitive Change

Outcome Measures

Primary Outcomes (1)

• Cognitive composite score (global score)

  When glucose levels have been stabilized for 40 minutes

Secondary Outcomes (1)

• Symbol Digit Modalities Test (SDMT)

  When glucose levels have been stabilized for 40 minutes

Study Arms (2)

Hyperketonemia - Placebo

EXPERIMENTAL

Participants are randomly assigned to initially receive ketone infusion and then saline infusion

Drug: Ketone infusion; Drug: Saline infusion

Placebo - Hyperketonemia

EXPERIMENTAL

Participants are randomly assigned to initially receive saline infusion and then ketone infusion

Drug: Ketone infusion; Drug: Saline infusion

Interventions

Ketone infusion DRUG

β-hydroxybutyrate is infused intravenously.

Hyperketonemia - Placebo; Placebo - Hyperketonemia

Saline infusion DRUG

saline is infused intravenously.

Hyperketonemia - Placebo; Placebo - Hyperketonemia

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• Psychiatric Centre Rigshospitalet: collaborator

Study Sites (1)

Department of Research in Endocrinology, Bispebjerg University Hospital

Copenhagen, Denmark

Location

MeSH Terms

Conditions

Ketosis

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical research assistant

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: September 5, 2018
• Study Start: September 17, 2018
• Primary Completion: February 14, 2019
• Study Completion: February 14, 2019
• Last Updated: February 20, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)