HypoglycaemiaHypoNeuroNCT01337362
Recurrent Hypoglycaemia in Type 1 Diabetes
A study testing Insulin clamp in people with Hypoglycaemia, run by Hillerod Hospital, Denmark at 1 site in Denmark.
Trial summary
Patients with type 1 diabetes are at risk of very low blood sugar levels (hypoglycaemia) as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia. During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoglycaemia
- What is being tested?
- Insulin clamp
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteDenmark
- Study dates
- May 2011to Jun 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes
- Age > 18 years
- - Have had diabetes for more than 5 years
- Negative pregnancy test
- Caucasian
- Signed written informed consent
Who cannot join
- Pregnant or breastfeeding
- Epilepsy
- Self-perceived impaired hearing
- Use of antiepileptic medicine
- Use of neuroleptics within the last 6 months
- Use of benzodiazepines within the last month
Show all 11Show fewer
- Use of betablockers
- Previous stroke or other disease in the brain
- Cardiovascular disease
- Alcohol-, drug- or medicine abuse
- Previous allergic reaction to heparin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Recurrent Hypoglycaemia in Type 1 Diabetes: Effects on Cognitive Function, Cerebral Electrical Activity, and Skin Temperature
Patients with type 1 diabetes are at risk of very low blood sugar levels (hypoglycaemia) as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia. During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines.
The purpose of the study is to investigate the activity in the brain, the cognitive function, and the skin temperature when patients are exposed to repeated hypoglycaemia. The results will show whether the response to hypoglycaemia will change after repeated episodes.
It is our hope that results can contribute to improved understanding of hypoglycaemic EEG changes.
Read the detailed description
Background:
Patients with type 1 diabetes are at risk of severe hypoglycaemia as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia (hypoglycaemia unawareness). The episodes are associated with impaired quality of life and can lead to permanent brain damage and death.
During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines. Repeated hypoglycaemic episodes result in down regulation of counter regulatory and symptomatic responses. It is not known whether a similar phenomenon is present for cerebral dysfunction as judged by EEG changes and cognitive function.
The purpose is to investigate the activity in the brain, the cognitive function, and the skin temperature when patients are exposed to repeated hypoglycaemia. The results will show whether the response to hypoglycaemia will change after repeated episodes.
The methods:
The investigators will recruit two groups of patients: Patients with hypoglycemia awareness and patients with hypoglycaemic unawareness.
The patients are exposed to hypoglycaemia on two concomitant days while the investigators record EEG and perform cognitive tests. Skin temperature is assessed by the use of thermography. If the patient has hypoglycaemic unawareness a 4 week period follows where the glycaemic control is loosened to avoid hypoglycaemia episodes and the patients is then exposed to hypoglycaemia again.
The prospect:
It is the investigators hope that results can contribute to improved understanding of hypoglycaemic EEG changes and skin temperature changes. This could be of potential benefit for patients with hypoglycaemic unawareness.
- Conditions
- Hypoglycaemia
- Being tested
- Insulin clamp
- Keywords
- Diabetes, Hypoglycaemia, EEG, Thermography, Hypoglycaemia-associated autonomic failure, QTc interval, Hypoglycemic alarm device, Hormone response
- Medical subject headings
- Hypoglycemia, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin clampProcedure or surgery
Also called Insulin, clamp
Patients will be exposed to low bloodsugar
| Study group | Role | What they receive |
|---|---|---|
| Patients with hypoglycemia awareness | Active comparator | Patients who have symptoms when the blood sugar level is low Receives: Procedure: Insulin clamp |
| patients with hypoglycaemic unawareness. | Experimental | Patients who do not feel any symptoms when the blood sugar levels are low Receives: Procedure: Insulin clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
EEG
EEG will be analysed in order to see whether there are any differences between aware and unaware patients during hypoglycaemia. It is our hope that the result can help develop an alarm before the patient experiences severe hypoglycaemia.
Measured: 2 years
Secondary outcomes (4)
QTc interval
The investigators want to investigate whether the QTc complex gets wider during hypoglycaemia. This is in order to see whether long QTc could be the explanation behind sudden dearth in diabetes patients.
Measured: 2 years
Skin temperature
Skin temperature will be measured by thermography. The investigators want to see whether the skin can be used as a biomarker for hypoglycaemia.
Measured: 2 years
Auditory evoked potentials
The investigators what to see whether there is any difference in auditory evoked potentials (AEP) between aware and unaware diabetic patients. The subject will hear a common and a rare sound in a 4:1 ratio while the EEG is recorded. Afterwards the data is analyzed and the AEPs are addressed.
Measured: 2 years
Cognitive function
The investigators want to address whether there are any differences in the cognitive function between aware and unaware patients. The cognitive function will be addressed by the use of cognitive function tests (CalCAP) and Stroops tests as well.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypoglycaemiaStudies 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hillerod Hospital, Denmark
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern Denmark, Copenhagen University Hospital, Rigshospitalet, UNEEG Medical A/S
- Responsible party
- Principal investigator, Anne-Sophie Sejling, Hillerod Hospital, Denmark
- Investigators
- Anne-Sophie Sejling, MD, Principal investigator, Hillerod Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01337362
- Sponsor's protocol ID
- H-1-2011-024
- Acronym
- HypoNeuro
- Status last verified
- Oct 2014
- First submitted
- 30 Mar 2011
- Last updated
- 16 Oct 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
She R, Al-Sari NH, Mattila IM, Sejling AS, Pedersen J, Legido-Quigley C, Pedersen-Bjergaard U. Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes. BMJ Open Diabetes Res Care. 2023 Jun;11(3):e003327. doi: 10.1136/bmjdrc-2023-003327.
PubMed 37369531Rubega M, Sparacino G, Sejling AS, Juhl CB, Cobelli C. Hypoglycemia-Induced Decrease of EEG Coherence in Patients with Type 1 Diabetes. Diabetes Technol Ther. 2016 Mar;18(3):178-84. doi: 10.1089/dia.2015.0347. Epub 2016 Jan 8.
PubMed 26745007
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recurrent Hypoglycaemia in Type 1 Diabetes: Effects on Cognitive Function, Cerebral Electrical Activity, and Skin Temperature
- ClinicalTrials.gov ID
- NCT01337362
- Acronym / sponsor ID
- HypoNeuro / H-1-2011-024
- Conditions
- Hypoglycaemia
- Keywords
- Diabetes, Hypoglycaemia, EEG, Thermography, Hypoglycaemia-associated autonomic failure, QTc interval, Hypoglycemic alarm device, Hormone response
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Hillerod Hospital, DenmarkUniversity, hospital or other
- Collaborators
- University of Southern Denmark, Copenhagen University Hospital, Rigshospitalet, UNEEG Medical A/S
- Study start
- May 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 18 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with type 1 diabetes are at risk of very low blood sugar levels (hypoglycaemia) as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia. During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines.
The purpose of the study is to investigate the activity in the brain, the cognitive function, and the skin temperature when patients are exposed to repeated hypoglycaemia. The results will show whether the response to hypoglycaemia will change after repeated episodes.
It is our hope that results can contribute to improved understanding of hypoglycaemic EEG changes.
Detailed description
Background:
Patients with type 1 diabetes are at risk of severe hypoglycaemia as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia (hypoglycaemia unawareness). The episodes are associated with impaired quality of life and can lead to permanent brain damage and death.
During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines. Repeated hypoglycaemic episodes result in down regulation of counter regulatory and symptomatic responses. It is not known whether a similar phenomenon is present for cerebral dysfunction as judged by EEG changes and cognitive function.
The purpose is to investigate the activity in the brain, the cognitive function, and the skin temperature when patients are exposed to repeated hypoglycaemia. The results will show whether the response to hypoglycaemia will change after repeated episodes.
The methods:
The investigators will recruit two groups of patients: Patients with hypoglycemia awareness and patients with hypoglycaemic unawareness.
The patients are exposed to hypoglycaemia on two concomitant days while the investigators record EEG and perform cognitive tests. Skin temperature is assessed by the use of thermography. If the patient has hypoglycaemic unawareness a 4 week period follows where the glycaemic control is loosened to avoid hypoglycaemia episodes and the patients is then exposed to hypoglycaemia again.
The prospect:
It is the investigators hope that results can contribute to improved understanding of hypoglycaemic EEG changes and skin temperature changes. This could be of potential benefit for patients with hypoglycaemic unawareness.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with hypoglycemia awareness | Active comparator | Procedure: Insulin clampPatients who have symptoms when the blood sugar level is low |
| patients with hypoglycaemic unawareness. | Experimental | Procedure: Insulin clampPatients who do not feel any symptoms when the blood sugar levels are low |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Type 1 diabetes
- Age > 18 years
- - Have had diabetes for more than 5 years
- Negative pregnancy test
- Caucasian
Key exclusion criteria (11 listed)
- Pregnant or breastfeeding
- Epilepsy
- Self-perceived impaired hearing
- Use of antiepileptic medicine
- Use of neuroleptics within the last 6 months
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 |
|---|---|---|
| Insulin clampAlso: Insulin, clampPatients will be exposed to low bloodsugar | Procedure or surgery | Patients with hypoglycemia awareness, patients with hypoglycaemic unawareness. |
Primary outcome
EEG
Time frame: 2 years
EEG will be analysed in order to see whether there are any differences between aware and unaware patients during hypoglycaemia. It is our hope that the result can help develop an alarm before the patient experiences severe hypoglycaemia.
4 secondary outcomes
QTc interval
Time frame: 2 years
Skin temperature
Time frame: 2 years
Auditory evoked potentials
Time frame: 2 years
Cognitive function
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2014.
- Derived from this study: PubMed 37369531She R, Al-Sari NH, Mattila IM, Sejling AS, Pedersen J, Legido-Quigley C, Pedersen-Bjergaard U. Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes. BMJ Open Diabetes Res Care. 2023 Jun;11(3):e003327. doi: 10.1136/bmjdrc-2023-003327.
- Derived from this study: PubMed 26745007Rubega M, Sparacino G, Sejling AS, Juhl CB, Cobelli C. Hypoglycemia-Induced Decrease of EEG Coherence in Patients with Type 1 Diabetes. Diabetes Technol Ther. 2016 Mar;18(3):178-84. doi: 10.1089/dia.2015.0347. Epub 2016 Jan 8.
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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.
Anne-Sophie Sejling, MD principal investigator
Hillerod Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insulin clamp in people with Hypoglycaemia, run by Hillerod Hospital, Denmark 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 6 inclusion and 11 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 16 Oct 2014. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
EEG (time frame: 2 years). 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 NCT01337362, which also lists 2 linked publications.
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 16 Oct 2014.