Diabetes Mellitus, Type IINCT03014011
Effects of Mild Hypoglycaemia on Cognitive Function in Type 2 Diabetes
A study testing Hypoglycaemic clamp and Euglycaemic clamp in people with Diabetes Mellitus, Type II and Hypoglycemia, run by Bispebjerg Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type II, Hypoglycemia, Cognitive Change
- What is being tested?
- Hypoglycaemic clamp and Euglycaemic clamp
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteDenmark
- Study dates
- 13 Jun 2017to 24 Jul 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 sulfonylureas, meglitinides or insulin.
- HbA1c ≤ 9.0 % by local laboratory analysis.
- BMI >23 kg/m2 and <35 kg/m2
Who cannot join
- 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.
Show all 18Show fewer
- Repeated resting blood pressure at screening outside the range 90-140 mmHg for systolic or 50-90 mmHg for diastolic. This exclusion criterion also pertains to subjects taking antihypertensives.
- 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.
- 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
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.
Read the detailed description
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. In healthy subjects a number of studies show that during a hypoglycaemic episode with plasma levels of 2.2 - 2.5 mmol/L (40-45 mg/dl) brain areas responsible for cognition have an altered neuronal function when measuring cerebral blood flow. This is accompanied by severely impaired cognitive function with a reduced ability to solve simple cognitive tasks. At higher levels of glucose (above 3 mmol/L (54 mg/dl)), it remains to be settled whether cognitive functions are also affected negatively and whether this may be accompanied by changes in brain metabolism. Apart from raising the blood glucose directly or indirectly via glucagon, no treatment for hypoglycaemia exists, but since Glucagon-like peptide-1 (GLP-1) based therapies used in type 2 diabetes may affect brain glucose consumption, therapeutic interventions to prevent negative results of hypoglycaemia may eventually become clinically possible.
Here, the investigators propose to provide quantitative results on cognition during an acute mild hypoglycaemic episode (target plasma glucose 3 mmol/L). Data will be provided on executive function, attention and memory.
- Conditions
- Diabetes Mellitus, Type II, Hypoglycemia, Cognitive Change
- Being tested
- Hypoglycaemic clamp, Euglycaemic clamp
- Medical subject headings
- Diabetes Mellitus, Type 2, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoglycaemic clampOther
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 clampOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Other: Hypoglycaemic clamp; Other: Euglycaemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2017 (estimated)
- Study start13 Jun 2017
- Primary completion23 Jul 2018
- Study completion24 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type IIStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, Psychiatric Centre Rigshospitalet
- Responsible party
- Principal investigator, Malin Nilsson, Bispebjerg Hospital
- Investigators
- Jørgen Rungby, Professor, Principal investigator, Department of Endocrinology, Bispebjerg University Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03014011
- Sponsor's protocol ID
- MISP
- Status last verified
- Dec 2019
- First submitted
- 21 Dec 2016
- Last updated
- 28 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31367958
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Mild Hypoglycaemia on Cognitive Function in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03014011
- Acronym / sponsor ID
- MISP
- Conditions
- Diabetes Mellitus, Type II, Hypoglycemia, Cognitive Change
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, Psychiatric Centre Rigshospitalet
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 23 Jul 2018 (actual)
- Study completion
- 24 Jul 2018 (actual)
- First posted
- 9 Jan 2017 (estimated)
- Results
- Posted 28 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. In healthy subjects a number of studies show that during a hypoglycaemic episode with plasma levels of 2.2 - 2.5 mmol/L (40-45 mg/dl) brain areas responsible for cognition have an altered neuronal function when measuring cerebral blood flow. This is accompanied by severely impaired cognitive function with a reduced ability to solve simple cognitive tasks. At higher levels of glucose (above 3 mmol/L (54 mg/dl)), it remains to be settled whether cognitive functions are also affected negatively and whether this may be accompanied by changes in brain metabolism. Apart from raising the blood glucose directly or indirectly via glucagon, no treatment for hypoglycaemia exists, but since Glucagon-like peptide-1 (GLP-1) based therapies used in type 2 diabetes may affect brain glucose consumption, therapeutic interventions to prevent negative results of hypoglycaemia may eventually become clinically possible.
Here, the investigators propose to provide quantitative results on cognition during an acute mild hypoglycaemic episode (target plasma glucose 3 mmol/L). Data will be provided on executive function, attention and memory.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoglycaemic clamp first, then euglyceamic clamp | Other | Other: Hypoglycaemic clamp, Other: Euglycaemic clampFirst 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). |
| Euglycaemic clamp first, then hypoglycaemic clamp | Other | Other: Hypoglycaemic clamp, Other: Euglycaemic clampFirst 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). |
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 sulfonylureas, meglitinides or insulin.
Key exclusion criteria (18 listed)
- 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.
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 |
|---|---|---|
| Hypoglycaemic clampThe 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. | Other | Euglycaemic clamp first, then hypoglycaemic clamp, Hypoglycaemic clamp first, then euglyceamic clamp |
| Euglycaemic clampThe 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. | Other | Euglycaemic clamp first, then hypoglycaemic clamp, Hypoglycaemic clamp first, then euglyceamic clamp |
Primary outcome
Psychomotor Speed
Time frame: 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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31367958Nilsson 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.
- 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.
Jørgen Rungby, Professor principal investigator
Department of Endocrinology, Bispebjerg University Hospital, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypoglycaemic clamp and Euglycaemic clamp in people with Diabetes Mellitus, Type II and Hypoglycemia, 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 28 Jan 2020. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Psychomotor Speed (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03014011, which also lists 1 linked publication.
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 28 Jan 2020.