Type1diabetesHypoADAPTNCT05095259
Metabolic Adaptation to High-frequent Hypoglycaemia in Type 1 Diabetes
A study testing insulin human, Epinephrin and Muscle biopsy in people with Type1diabetes, run by Nordsjaellands Hospital at 2 sites in Denmark.
Trial summary
An experimental mechanistic study. The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Type1diabetes
- What is being tested?
- insulin human, Epinephrin and Muscle biopsy
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesDenmark
- Study dates
- 16 Dec 2019to Dec 2023
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent
- Male or female aged 18-70 years
- Must be able to speak and read Danish
- Type 1 diabetes patients or healthy individuals (control goup)
- A documented clinically relevant history of type 1 diabetes
- In insulin treatment regimen
- The subject must be willing and able to comply with trial protocol
Who cannot join
- History of severe psychological condition
- History of severe heart disease
- History of epilepsy, former apoplexies and dementia
- History of muscle diseases
- History of liver disease
- History of malignancy unless a disease-free period exceeding 5 years
Show all 9Show fewer
- Implants not compatible for MRI scans
- History of alcohol or drug abuse
- Pregnant or lactating woman
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Steno Diabetes Center Copenhagen
Gentofte Municipality, 2820
Nordsjaellands Hospital
Hillerød, 3400
About this study
Official title: Metabolic Adaptation to High-frequent Hypoglycaemia in Type 1 Diabetes - the HypoADAPT Study
An experimental mechanistic study. The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. The knowledge to be obtained may feed into experimental hypoglycaemic clamp studies to further elucidate the effect of the adaptations during acute hypoglycaemia. Ultimately, it may lead to intervention studies aiming at the maintenance of functional capability during hypoglycaemia in patients with type 1 diabetes to reduce their risk of severe hypoglycaemia.
Read the detailed description
Study rationale The risk of severe hypoglycaemia is a major daily concern for people with diabetes treated with insulin. Severe hypoglycaemia is the main barrier in achieving the recommended glycaemic targets and may indirectly be the main driver for late diabetic complications and related morbidity, mortality and health care costs. In people with diabetes, recurrent exposure to insulin-induced mild hypoglycaemia leads to significant adaptive physiologic responses. While the metabolism of the brain and hormonal responses to hypoglycaemia have been studied extensively, this study will as the first, systematically investigate the chronic adaptation of peripheral metabolism to recurrent hypoglycaemia in diabetes. Knowledge about such responses can lead to interventions that attenuate the devastating effects of acute hypoglycaemia induced by insulin in people with diabetes. Thereby, the risk of developing severe hypoglycaemia can be reduced which ultimately will improve long-term diabetes outcomes and reduce health care costs.
Hypothesis Patients with type 1 diabetes that are exposed to high-frequent recurrent hypoglycaemia will adapt their metabolism in a way, which supports the preservation of brain fuelling.
Objectives
Primary objective The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. The knowledge to be obtained may feed into experimental hypoglycaemic clamp studies to further elucidate the effect of the adaptations during acute hypoglycaemia. Ultimately, it can lead to intervention studies aiming at the maintenance of functional capability during hypoglycaemia in patients with type 1 diabetes to reduce their risk of severe hypoglycaemia.
Secondary objectives
- To study the metabolic consequences of recurrent hypoglycaemia in the brain, liver, muscle and adipose tissues
- To study the consequences of recurrent hypoglycaemia on resting metabolic rest
- To study the consequences of recurrent hypoglycaemia on glucagon and adrenaline sensitivity
- To study the consequences of recurrent hypoglycaemia on epigenetic profiles
- To study the consequences of recurrent hypoglycaemia on oxidative stress
- To study the psychological factors associated with recurrent hypoglycaemia
- Conditions
- Type1diabetes
- Being tested
- insulin human, Epinephrin, Muscle biopsy, Adipose tissue biopsy, Glucagon
- Keywords
- Diabetes Complications, Hypoglycemia, Metabolism
- Medical subject headings
- Diabetes Complications, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
insulin humanDrug
Also called Actrapid
Hyperinsulinemic glucose clamp studies require that insulin is administered at a steady continuous rate to achieve stable levels of hyperinsulinemia. To reach this, insulin needs to be infused intravenously using a standard intravenous pump system. The insulin dose will be adjusted according to the body surface area, aiming for insulin levels of ~170 mIU/l, which is within the physiological range. Thus, for a subject with a bodyweight of 70 kg, body length of 180 cm and - consequently - a body surface area of 1.936 m2, the required insulin infusion can be calculated as: 1.936 x 60 x 60 ÷ 1000 = 7.0 units per hour
EpinephrinDrug
Also called Adrenalin
Epinephrine are prepared in 100 ml isotone saline solution according to weight and infused in 3 different infusion rates: 10 ng∙kg-1∙min-1, 25 ng∙kg-1∙min-1 and 50 ng∙kg-1∙min-1, for 20 minutes each. After each adrenaline infusion, substrate response will be measured by blood samples of glucose, lactate, free fatty acids, alanine, β-hydroxybutyrate, glycerol and insulin. Furthermore, cardiovascular measurements such as pulse and blood pressure are monitored as well.
Muscle biopsyProcedure or surgery
With the study subject resting in the supine position, the skin is disinfected on the lateral side of the thigh around 15 cm above the knee, with chlorhexidine alcohol. Then 3-4 mL of local anaesthetic (lidocaine 20 mg/mL) is injected into the skin, subcutaneous tissue and in the upper part of the muscle with a very thin needle. When the anaesthetic effect has set in after a couple of minutes an insertion is made in the skin and the subcutaneous tissue through which the biopsy cannula is inserted into the muscle. A small piece (around 150 mg) of the muscle is collected, which may be experienced as somewhat unpleasant, but will last for a very short while ( ~1-2 seconds). The needle is removed, a sterile Band-Aid is applied, and the study subject can leave the site after termination of the trial. The biopsy may cause some muscular tenderness for 2-3 days corresponding to minor muscular trauma.
Adipose tissue biopsyProcedure or surgery
With the study subject resting in the supine position, the skin is disinfected on one side of the abdomen around 5-10 cm lateral from the umbilicus to the knee, with chlorhexidine alcohol. Then 3-4 mL of local anaesthetic (lidocaine 20 mg/mL) is injected into the skin, subcutaneous tissue and in the upper part of the adipose tissue with a very thin needle. When the anaesthetic effect has set in after a couple of minutes an insertion is made in the skin and the subcutaneous tissue through which the biopsy cannula is inserted into the adipose tissue. A small piece (around 1 gram) of the adipose tissue is collected, which may be experienced as somewhat unpleasant, but will last for a very short while ( ~1-2 seconds). The needle is removed, a sterile Band-Aid is applied, and the study subject can leave the site after termination of the trial. The biopsy may cause some tenderness for 2-3 days corresponding to minor trauma.
GlucagonDrug
Also called GlucaGen
Glucagon is prepared in doses of 10 µg, 25 µg, and 50 µg and intravenously injected with intervals of 2 hours. After each glucagon injection, blood samples will be drawn to measure plasma glucose, glucagon, lactate, free fatty acids, alanine, amino-acids, β-hydroxybutyrate, glycerol and insulin. Furthermore, cardiovascular measurements such as pulse and blood pressure are monitored as well.
IPRO 2 Medtronic MinimedDevice
Also called Blinded Continuous Glucose Monitoring
All potential subjects will receive a blinded continuous glucose sensor at Visit 1. At the following visits, the continuous glucose monitor (CGM) will be reviewed for hypoglycaemia episodes and replaced at the same time. At Visit 2 a final screening of the inclusion criteria will take place, which involves the CGM data of the first week. A blinded CGM will be installed a week before every visit.
7 Tesla (7T) Magnetic Resonance ImagingProcedure or surgery
Also called 7T MRI
Subjects will undergo a hyperinsulinemic euglycaemic glucose clamp, as mentioned above, in the MRI scanning room. After 30 minutes of stable normoglycaemia, subjects are taken into the MRI scanner (Philips Achieva 7.0 T) where brain, liver, thigh and calf muscle are scanned. After every anatomically different area, the subjects must be taken out of the scanner, while scanning coils are replaced. All subjects are advised to lie still and press the alarm button if necessary.
Indirect Calorimetry using Jaeger Oxycon ChampionProcedure or surgery
Resting metabolic rate will be estimated, after reaching stable plasma glucose level, via a hyperinsulinemic euglycaemic clamp, as mentioned above. This will be done by indirect calorimetry, using a ventilated hood system (Jaeger Oxycon Champion, software version 4.3, Jaeger, Mijnhardt). Subjects are instructed to lie down and rest for a period of 30 minutes. Subjects are also instructed not to move, talk or sleep unless necessary during the period of measurement. The recorded measurement after 5 minutes to 30 minutes will be used for analysis.
Core temperature and thermography using Thermovision SC645Procedure or surgery
Thermography (Thermovision SC645, FLIR Systems, Wilsonville, OR, USA) is used to determine cutaneous vascular perfusion. Data is analogue-digital converted and sampled at 100 Hz (Powerlab, ADInstruments, Colorado Springs, CO, USA).
Freestyle Libre 2Device
Also called Intermittently scanned continuous glucose monitor
All potential subjects will receive a continuous glucose sensor at Visit 1. At the following visits, the CGM will be reviewed for hypoglycaemia episodes and replaced at the same time. At Visit 2 a final screening of the inclusion criteria will take place, which involves the CGM data of the first week. A CGM will be installed a week before every visit.
| Study group | Role | What they receive |
|---|---|---|
| Participants with Type 1 Diabetes Mellitus | Experimental | Participants with Type 1 Diabetes Mellitus Receives: Drug: insulin human; Drug: Epinephrin; Procedure: Muscle biopsy; Procedure: Adipose tissue biopsy; Drug: Glucagon; Device: IPRO 2 Medtronic Minimed; Procedure: 7 Tesla (7T) Magnetic Resonance Imaging; Procedure: Indirect Calorimetry using Jaeger Oxycon Champion; Procedure: Core temperature and thermography using Thermovision SC645; Device: Freestyle Libre 2 |
| Healthy Controls | Active comparator | Healthy Controls Receives: Drug: insulin human; Drug: Epinephrin; Procedure: Muscle biopsy; Procedure: Adipose tissue biopsy; Drug: Glucagon; Device: IPRO 2 Medtronic Minimed; Procedure: 7 Tesla (7T) Magnetic Resonance Imaging; Procedure: Indirect Calorimetry using Jaeger Oxycon Champion; Procedure: Core temperature and thermography using Thermovision SC645 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolite- and lipid profiling
Metabolite- and lipid profiling of blood samples using metabolomics profiling platforms during euglycaemia
Measured: 5 minutes
Brain lactate concentration
Brain lactate concentration using non-invasive magnetic resonance (MR) spectroscopy during euglycaemia
Measured: 20 minutes
Brain adenosine triphosphate (ATP) concentration
Brain ATP concentration using non-invasive MR spectroscopy during euglycaemia
Measured: 20 minutes
Glycogen in muscle and adipose tissue
Glycogen in muscle and adipose tissue biopsies during euglycaemia
Measured: 5 minutes
Non-specific proteins in muscle and adipose tissue
Non-specific proteins in muscle and adipose tissue biopsies during euglycaemia
Measured: 5 minutes
Glycogen concentration
Glycogen in liver and muscle tissue using non-invasive MR spectroscopy during euglycaemia.
Measured: 40 minutes
Secondary outcomes (29)
Estimated glucose production during glucagon stimulation
Area under the curve (AUC) for plasma glucose during glucagon injections. Plasma glucose measurement
Measured: Every 5 minutes up to 5 hours
Estimated glucose production during epinephrine stimulation
Area under the curve (AUC) for plasma glucose during epinephrine infusion. Plasma glucose measurement
Measured: Every 5 minutes up to 90 minutes
Indirect calorimetry
Estimating resting metabolic rate, before and during hyperinsulinemic-hypoglycemic clamp
Measured: 60 minutes
Thermography
Estimating skin temperature, before and during hyperinsulinemic-hypoglycemic clamp
Measured: 5 minutes
Plasma lactate during glucagon injections.
Plasma lactate during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma free fatty acids during glucagon injections.
Plasma free fatty acids during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma glycerol during glucagon injections.
Plasma glycerol during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma alanine during glucagon injections.
Plasma alanine during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma β-hydroxybutyrate during glucagon injections.
Plasma β-hydroxybutyrate during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma insulin during glucagon injections.
Plasma insulin during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma glucagon during glucagon injections.
Plasma glucagon during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma metabolomics during glucagon injections.
Plasma metabolomics during glucagon injections.
Measured: Every 40 minutes up to 5 hours
Plasma lactate during epinephrine infusion
Plasma lactate during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma free fatty acids during epinephrine infusion
Plasma free fatty acids during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma glycerol during epinephrine infusion
Plasma glycerol during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma alanine during epinephrine infusion
Plasma alanine during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma β-hydroxybutyrate during epinephrine infusion
Plasma β-hydroxybutyrate during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma insulin during epinephrine infusion
Plasma insulin during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma glucagon during epinephrine infusion
Plasma glucagon during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma epinephrine during epinephrine infusion
Plasma catecholamines during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma norepinephrine during epinephrine infusion
Plasma catecholamines during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Plasma metabolomics during epinephrine infusion
Plasma metabolomics during epinephrine infusion
Measured: Every 20 minutes up to 90 minutes
Personality traits using the psychometry questionnaire Type D Scale-14 (DS-14)
Personality traits using the psychometry questionnaire DS-14, score between 0-28, the higher, the more likely they have type D personality
Measured: 30 minutes
Personality traits using the psychometry questionnaire Toronto Alexithymia Scale (TAS-20)
Personality traits using the psychometry questionnaire TAS-20, score 20-100, the higher score the more likely they are alexithymia
Measured: 30 minutes
Diabetes and hypoglycaemia status using psychometry questionnaire Hypoglycemia Fear Survey - Worry (HFS-W)
Diabetes and hypoglycaemia status using psychometry questionnaire HFS-W, score 0-72, the higher score the higher fear for hypoglycemia
Measured: 30 minutes
Diabetes and hypoglycaemia status using psychometry questionnaire Hypoglycemia Attitudes and Behavior Scale (HABS)
Diabetes and hypoglycaemia status using psychometry questionnaire HABS, score from 14-45, higher score more fear of hypoglycemia
Measured: 30 minutes
Diabetes and hypoglycaemia status using psychometry questionnaire Problem Areas in Diabetes (PAID)
Diabetes and hypoglycaemia status using psychometry questionnaire PAID, 0-80, the higher score, the more problems with diabetes
Measured: 30 minutes
Food consumption
Using Food Frequency Questionnaire to analyze food consumption
Measured: 30 minutes
Hypoglycemia awareness status
Using hypoglycemia awareness status questionnaire
, 0-7, higher score indicate hypoglycemia unawareness
Measured: 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2021
- Study start16 Dec 2019
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type1diabetesStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Experimental Observational Case-Control study. Two groups: One group of type 1 diabetes and one group of healthy controls.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nordsjaellands Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Research Centre for Magnetic Resonance, University of Copenhagen, Steno Diabetes Center Copenhagen
- Responsible party
- Sponsor
- Investigators
- Ulrik Pedersen-Bjergaard, MD,PhD,Prof, Principal investigator, Nordsjaellands Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05095259
- Sponsor's protocol ID
- DRCMR7T-06
- Other IDs
- 2019-001938-34, 2019
- Acronym
- HypoADAPT
- Status last verified
- Feb 2023
- First submitted
- 1 Oct 2021
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
She R, Suvitaival T, Andersen HU, Hommel E, Norgaard K, Wojtaszewski JFP, Legido-Quigley C, Pedersen-Bjergaard U. Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals. Diabetologia. 2024 Jun;67(6):1095-1106. doi: 10.1007/s00125-024-06116-5. Epub 2024 Mar 1.
PubMed 38427076
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Adaptation to High-frequent Hypoglycaemia in Type 1 Diabetes - the HypoADAPT Study
- ClinicalTrials.gov ID
- NCT05095259
- Acronym / sponsor ID
- HypoADAPT / DRCMR7T-06
- Conditions
- Type1diabetes
- Keywords
- Diabetes Complications, Hypoglycemia, Metabolism
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Nordsjaellands HospitalUniversity, hospital or other
- Collaborators
- Danish Research Centre for Magnetic Resonance, University of Copenhagen, Steno Diabetes Center Copenhagen
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 27 Oct 2021 (actual)
- 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.
An experimental mechanistic study. The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. The knowledge to be obtained may feed into experimental hypoglycaemic clamp studies to further elucidate the effect of the adaptations during acute hypoglycaemia. Ultimately, it may lead to intervention studies aiming at the maintenance of functional capability during hypoglycaemia in patients with type 1 diabetes to reduce their risk of severe hypoglycaemia.
Detailed description
Study rationale The risk of severe hypoglycaemia is a major daily concern for people with diabetes treated with insulin. Severe hypoglycaemia is the main barrier in achieving the recommended glycaemic targets and may indirectly be the main driver for late diabetic complications and related morbidity, mortality and health care costs. In people with diabetes, recurrent exposure to insulin-induced mild hypoglycaemia leads to significant adaptive physiologic responses. While the metabolism of the brain and hormonal responses to hypoglycaemia have been studied extensively, this study will as the first, systematically investigate the chronic adaptation of peripheral metabolism to recurrent hypoglycaemia in diabetes. Knowledge about such responses can lead to interventions that attenuate the devastating effects of acute hypoglycaemia induced by insulin in people with diabetes. Thereby, the risk of developing severe hypoglycaemia can be reduced which ultimately will improve long-term diabetes outcomes and reduce health care costs.
Hypothesis Patients with type 1 diabetes that are exposed to high-frequent recurrent hypoglycaemia will adapt their metabolism in a way, which supports the preservation of brain fuelling.
Objectives
Primary objective The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. The knowledge to be obtained may feed into experimental hypoglycaemic clamp studies to further elucidate the effect of the adaptations during acute hypoglycaemia. Ultimately, it can lead to intervention studies aiming at the maintenance of functional capability during hypoglycaemia in patients with type 1 diabetes to reduce their risk of severe hypoglycaemia.
Secondary objectives
- To study the metabolic consequences of recurrent hypoglycaemia in the brain, liver, muscle and adipose tissues
- To study the consequences of recurrent hypoglycaemia on resting metabolic rest
- To study the consequences of recurrent hypoglycaemia on glucagon and adrenaline sensitivity
- To study the consequences of recurrent hypoglycaemia on epigenetic profiles
- To study the consequences of recurrent hypoglycaemia on oxidative stress
- To study the psychological factors associated with recurrent hypoglycaemia
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Experimental Observational Case-Control study. Two groups: One group of type 1 diabetes and one group of healthy controls.
| Arm | Type | Receives |
|---|---|---|
| Participants with Type 1 Diabetes Mellitus | Experimental | Drug: insulin human, Drug: Epinephrin, Procedure: Muscle biopsy, Procedure: Adipose tissue biopsy, Drug: Glucagon, Device: IPRO 2 Medtronic Minimed, Procedure: 7 Tesla (7T) Magnetic Resonance Imaging, Procedure: Indirect Calorimetry using Jaeger Oxycon Champion, Procedure: Core temperature and thermography using Thermovision SC645, Device: Freestyle Libre 2Participants with Type 1 Diabetes Mellitus |
| Healthy Controls | Active comparator | Drug: insulin human, Drug: Epinephrin, Procedure: Muscle biopsy, Procedure: Adipose tissue biopsy, Drug: Glucagon, Device: IPRO 2 Medtronic Minimed, Procedure: 7 Tesla (7T) Magnetic Resonance Imaging, Procedure: Indirect Calorimetry using Jaeger Oxycon Champion, Procedure: Core temperature and thermography using Thermovision SC645Healthy Controls |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ability to provide written informed consent
- Male or female aged 18-70 years
- Must be able to speak and read Danish
- Type 1 diabetes patients or healthy individuals (control goup)
- A documented clinically relevant history of type 1 diabetes
Key exclusion criteria (9 listed)
- History of severe psychological condition
- History of severe heart disease
- History of epilepsy, former apoplexies and dementia
- History of muscle diseases
- History of liver 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 |
|---|---|---|
| insulin humanAlso: ActrapidHyperinsulinemic glucose clamp studies require that insulin is administered at a steady continuous rate to achieve stable levels of hyperinsulinemia. To reach this, insulin needs to be infused intravenously using a standard intravenous pump system. The insulin dose will be adjusted according to the body surface area, aiming for insulin levels of ~170 mIU/l, which is within the physiological range. Thus, for a subject with a bodyweight of 70 kg, body length of 180 cm and - consequently - a body surface area of 1.936 m2, the required insulin infusion can be calculated as: 1.936 x 60 x 60 ÷ 1000 = 7.0 units per hour | Drug | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| EpinephrinAlso: AdrenalinEpinephrine are prepared in 100 ml isotone saline solution according to weight and infused in 3 different infusion rates: 10 ng∙kg-1∙min-1, 25 ng∙kg-1∙min-1 and 50 ng∙kg-1∙min-1, for 20 minutes each. After each adrenaline infusion, substrate response will be measured by blood samples of glucose, lactate, free fatty acids, alanine, β-hydroxybutyrate, glycerol and insulin. Furthermore, cardiovascular measurements such as pulse and blood pressure are monitored as well. | Drug | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| Muscle biopsyWith the study subject resting in the supine position, the skin is disinfected on the lateral side of the thigh around 15 cm above the knee, with chlorhexidine alcohol. Then 3-4 mL of local anaesthetic (lidocaine 20 mg/mL) is injected into the skin, subcutaneous tissue and in the upper part of the muscle with a very thin needle. When the anaesthetic effect has set in after a couple of minutes an insertion is made in the skin and the subcutaneous tissue through which the biopsy cannula is inserted into the muscle. A small piece (around 150 mg) of the muscle is collected, which may be experienced as somewhat unpleasant, but will last for a very short while ( ~1-2 seconds). The needle is removed, a sterile Band-Aid is applied, and the study subject can leave the site after termination of the trial. The biopsy may cause some muscular tenderness for 2-3 days corresponding to minor muscular trauma. | Procedure or surgery | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| Adipose tissue biopsyWith the study subject resting in the supine position, the skin is disinfected on one side of the abdomen around 5-10 cm lateral from the umbilicus to the knee, with chlorhexidine alcohol. Then 3-4 mL of local anaesthetic (lidocaine 20 mg/mL) is injected into the skin, subcutaneous tissue and in the upper part of the adipose tissue with a very thin needle. When the anaesthetic effect has set in after a couple of minutes an insertion is made in the skin and the subcutaneous tissue through which the biopsy cannula is inserted into the adipose tissue. A small piece (around 1 gram) of the adipose tissue is collected, which may be experienced as somewhat unpleasant, but will last for a very short while ( ~1-2 seconds). The needle is removed, a sterile Band-Aid is applied, and the study subject can leave the site after termination of the trial. The biopsy may cause some tenderness for 2-3 days corresponding to minor trauma. | Procedure or surgery | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| GlucagonAlso: GlucaGenGlucagon is prepared in doses of 10 µg, 25 µg, and 50 µg and intravenously injected with intervals of 2 hours. After each glucagon injection, blood samples will be drawn to measure plasma glucose, glucagon, lactate, free fatty acids, alanine, amino-acids, β-hydroxybutyrate, glycerol and insulin. Furthermore, cardiovascular measurements such as pulse and blood pressure are monitored as well. | Drug | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| IPRO 2 Medtronic MinimedAlso: Blinded Continuous Glucose MonitoringAll potential subjects will receive a blinded continuous glucose sensor at Visit 1. At the following visits, the continuous glucose monitor (CGM) will be reviewed for hypoglycaemia episodes and replaced at the same time. At Visit 2 a final screening of the inclusion criteria will take place, which involves the CGM data of the first week. A blinded CGM will be installed a week before every visit. | Device | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| 7 Tesla (7T) Magnetic Resonance ImagingAlso: 7T MRISubjects will undergo a hyperinsulinemic euglycaemic glucose clamp, as mentioned above, in the MRI scanning room. After 30 minutes of stable normoglycaemia, subjects are taken into the MRI scanner (Philips Achieva 7.0 T) where brain, liver, thigh and calf muscle are scanned. After every anatomically different area, the subjects must be taken out of the scanner, while scanning coils are replaced. All subjects are advised to lie still and press the alarm button if necessary. | Procedure or surgery | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| Indirect Calorimetry using Jaeger Oxycon ChampionResting metabolic rate will be estimated, after reaching stable plasma glucose level, via a hyperinsulinemic euglycaemic clamp, as mentioned above. This will be done by indirect calorimetry, using a ventilated hood system (Jaeger Oxycon Champion, software version 4.3, Jaeger, Mijnhardt). Subjects are instructed to lie down and rest for a period of 30 minutes. Subjects are also instructed not to move, talk or sleep unless necessary during the period of measurement. The recorded measurement after 5 minutes to 30 minutes will be used for analysis. | Procedure or surgery | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| Core temperature and thermography using Thermovision SC645Thermography (Thermovision SC645, FLIR Systems, Wilsonville, OR, USA) is used to determine cutaneous vascular perfusion. Data is analogue-digital converted and sampled at 100 Hz (Powerlab, ADInstruments, Colorado Springs, CO, USA). | Procedure or surgery | Healthy Controls, Participants with Type 1 Diabetes Mellitus |
| Freestyle Libre 2Also: Intermittently scanned continuous glucose monitorAll potential subjects will receive a continuous glucose sensor at Visit 1. At the following visits, the CGM will be reviewed for hypoglycaemia episodes and replaced at the same time. At Visit 2 a final screening of the inclusion criteria will take place, which involves the CGM data of the first week. A CGM will be installed a week before every visit. | Device | Participants with Type 1 Diabetes Mellitus |
Primary outcome
Metabolite- and lipid profiling
Time frame: 5 minutes
Metabolite- and lipid profiling of blood samples using metabolomics profiling platforms during euglycaemia
Brain lactate concentration
Time frame: 20 minutes
Brain lactate concentration using non-invasive magnetic resonance (MR) spectroscopy during euglycaemia
Brain adenosine triphosphate (ATP) concentration
Time frame: 20 minutes
Brain ATP concentration using non-invasive MR spectroscopy during euglycaemia
Glycogen in muscle and adipose tissue
Time frame: 5 minutes
Glycogen in muscle and adipose tissue biopsies during euglycaemia
Non-specific proteins in muscle and adipose tissue
Time frame: 5 minutes
Non-specific proteins in muscle and adipose tissue biopsies during euglycaemia
Glycogen concentration
Time frame: 40 minutes
Glycogen in liver and muscle tissue using non-invasive MR spectroscopy during euglycaemia.
29 secondary outcomes
Estimated glucose production during glucagon stimulation
Time frame: Every 5 minutes up to 5 hours
Estimated glucose production during epinephrine stimulation
Time frame: Every 5 minutes up to 90 minutes
Indirect calorimetry
Time frame: 60 minutes
Thermography
Time frame: 5 minutes
Plasma lactate during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma free fatty acids during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma glycerol during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma alanine during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma β-hydroxybutyrate during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma insulin during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma glucagon during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma metabolomics during glucagon injections.
Time frame: Every 40 minutes up to 5 hours
Plasma lactate during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma free fatty acids during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma glycerol during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma alanine during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma β-hydroxybutyrate during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma insulin during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma glucagon during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma epinephrine during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma norepinephrine during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Plasma metabolomics during epinephrine infusion
Time frame: Every 20 minutes up to 90 minutes
Personality traits using the psychometry questionnaire Type D Scale-14 (DS-14)
Time frame: 30 minutes
Personality traits using the psychometry questionnaire Toronto Alexithymia Scale (TAS-20)
Time frame: 30 minutes
Diabetes and hypoglycaemia status using psychometry questionnaire Hypoglycemia Fear Survey - Worry (HFS-W)
Time frame: 30 minutes
Diabetes and hypoglycaemia status using psychometry questionnaire Hypoglycemia Attitudes and Behavior Scale (HABS)
Time frame: 30 minutes
Diabetes and hypoglycaemia status using psychometry questionnaire Problem Areas in Diabetes (PAID)
Time frame: 30 minutes
Food consumption
Time frame: 30 minutes
Hypoglycemia awareness status
Time frame: 10 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Derived from this study: PubMed 38427076She R, Suvitaival T, Andersen HU, Hommel E, Norgaard K, Wojtaszewski JFP, Legido-Quigley C, Pedersen-Bjergaard U. Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals. Diabetologia. 2024 Jun;67(6):1095-1106. doi: 10.1007/s00125-024-06116-5. Epub 2024 Mar 1.
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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.
Ulrik Pedersen-Bjergaard, MD,PhD,Prof principal investigator
Nordsjaellands Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing insulin human, Epinephrin and Muscle biopsy in people with Type1diabetes, run by Nordsjaellands Hospital at 2 sites 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 9 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: status not confirmed, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Results are not available in the source record.
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?
Metabolite- and lipid profiling (time frame: 5 minutes). The study lists 6 primary outcomes in all. 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 NCT05095259, 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 3 May 2023.