Effects of Mild Hypoglycaemia on Cognitive Function in Type 2 Diabetes

NCT03014011 | Completed Results DMC

• 1 other identifier: MISP
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Hypoglycaemia in subjects suffering from type 2 diabetes may have substantial consequences including a significant negative impact on quality of life. Further, repeated minor hypoglycaemias may result in significant productivity losses. Here, the investigators propose to provide quantitative results on cognition during an acute mild hypoglycaemic episode (target plasma glucose 3 mmol/L) in 28 subjects with type 2 diabetes. Data will be provided on executive function, attention and memory.

Conditions

Diabetes Mellitus, Type II; Hypoglycemia; Cognitive Change

Outcome Measures

Primary Outcomes (1)

• Psychomotor Speed

  Symbol Digit Modalities Test was used as a measurement of psychomotor speed. For the Symbol Digit Modalities Test, participants were required to use a coded key to match nine abstract symbols paired with numerical digits. The final score is the correct number of substitutions in 120 s, and scores range between 0 and 110. Higher values represent a better outcome.

  All neurocognitive testing was assessed at each intervention when glucose levels had been stabile for 40 minutes, an average of 2 hours after clamp procedure start. The duration of neurocognitive testing was approximately 40 min.

Study Arms (2)

Hypoglycaemic clamp first, then euglyceamic clamp

OTHER

First intervention with a hypoglycaemic clamp (one examination day of approximately 5 hours), there after a wash out period of 21-42 days, then second and final intervention day with an euglycaemic clamp (approximately 5 hours).

Other: Hypoglycaemic clamp; Other: Euglycaemic clamp

Euglycaemic clamp first, then hypoglycaemic clamp

OTHER

First intervention with an euglycaemic clamp (one examination day of approximately 5 hours), there after a wash out period of 21-42 days, then second and final intervention day with a hypoglycaemic clamp (approximately 5 hours).

Other: Hypoglycaemic clamp; Other: Euglycaemic clamp

Interventions

Hypoglycaemic clamp OTHER

The clamp is performed by insulin and adjustable 20% glucose infusions, with the aim to lower and keep plasma blood glucose levels at 3 mmol/L for outcome measurements.

Euglycaemic clamp first, then hypoglycaemic clamp; Hypoglycaemic clamp first, then euglyceamic clamp

Euglycaemic clamp OTHER

The clamp is performed by insulin and adjustable 20% glucose infusions, with the aim to keep plasma blood glucose levels at 6 mmol/L for outcome measurements.

Euglycaemic clamp first, then hypoglycaemic clamp; Hypoglycaemic clamp first, then euglyceamic clamp

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 sulfonylureas, meglitinides or insulin.
• HbA1c ≤ 9.0 % 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 before screening in this trial.
• 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.
• Visual impairment 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 3 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
• University Hospital, Gentofte, Copenhagen: collaborator
• Psychiatric Centre Rigshospitalet: collaborator

Study Sites (1)

Department of Research in Endocrinology, Bispebjerg University Hospital

Copenhagen, Denmark

Location

Related Publications (1)

• Nilsson M, Jensen N, Gejl M, Bergmann ML, Storgaard H, Zander M, Miskowiak K, Rungby J. Experimental non-severe hypoglycaemia substantially impairs cognitive function in type 2 diabetes: a randomised crossover trial. Diabetologia. 2019 Oct;62(10):1948-1958. doi: 10.1007/s00125-019-4964-4. Epub 2019 Jul 31.

  PMID: 31367958 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Interventions

Glucose Clamp Technique

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: MD Malin Nilsson
• Organization: Bispebjerg Hospital

mnil0028@regionh.dk

50595861

Study Officials

• Jørgen Rungby, Professor

  Department of Endocrinology, Bispebjerg University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: January 9, 2017
• Study Start: June 13, 2017
• Primary Completion: July 23, 2018
• Study Completion: July 24, 2018
• Last Updated: January 28, 2020
• Results First Posted: January 28, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)