Type 1 Diabetes MellitusPhase 2PILOT_EGPNCT02028078
Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemia
A Phase 2 study testing Insulin human in people with Type 1 Diabetes Mellitus, run by Medical University of Graz at 1 site in Austria.
Trial summary
Primary objective is to investigate the feasibility and stability of determining the endogenous glucose production during a hypoglycaemic clamp in type 1 diabetes mellitus subjects by a stable tracer to tracee ratio with an enrichment of 4% and a variation below +/-30%. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Insulin human
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteAustria
- Study dates
- Jan 2014to Mar 2016
- Phase
- Phase 2
- 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 1.)Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- 2. )Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months prior to screening visit 3.)Male or female, aged 18 - 64 years (both inclusive) 4.) Body mass index (BMI) 18.0 - 28.0 kg/m2 (both inclusive) 5.) HbA1c 42 - 80 mmol/mol (6.0-9.5%) 6. )Treated with daily insulin injections or continuous s.c. insulin infusion (CSII) ≥ 12 months. Stable insulin dose as judged by the investigator.
Who cannot join
- Known or suspected hypersensitivity to trial product(s) or related products
- Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) as judged by the investigator
- Severe hypoglycaemia within 1 month of screening
- Hypoglycaemia unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
- Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the investigator and any of the following laboratory safety results:
- ASAT, ALAT, lipase, alkaline phosphatase > 2.0 times upper limit of reference range (ULN)
Show all 32Show fewer
- Haemoglobin < 8.0 mmol/L (male) or < 6.4 mmol/L (female), total leukocyte count < 3.0 x 109/L, thrombocytes <100 x 109/L
- Serum creatinine levels ≥ 126 μmol/L (male) or ≥ 111 μmol/L (female)
- Suffer from or history of a life threatening disease (e.g. cancer except basal cell skin cancer or squamous cell skin cancer), or any clinically significant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (with the exception of diabetes mellitus and euthyroid struma), haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders as judged by the investigator.
- 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 prior to screening and/or acute myocardial infarction at any time.
- Supine blood pressure at screening (after resting for 5 min) outside the range of 90-140 mmHg for systolic or 50-90 mmHg for diastolic (repeated measurement on a second screening visit allowed to exclude white-coat hypertension). This exclusion criterion also pertains to subjects being on antihypertensives.
- Clinically significant abnormal ECG at screening, as judged by the investigator.
- Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the investigator.
- Any disease or condition that, in the opinion of the investigator, would represent an unacceptable risk for the subject's safety.
- Subject positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies (or diagnosed with active hepatitis according to local practice).
- Positive result of the screening test for HIV-1 antibodies, HIV-2 antibodies and/or HIV-1 antigen according to locally used diagnostic testing.
- History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
- Subject who has donated any blood or plasma in the past month or more than 500 mL within 3 months prior to screening.
- Surgery or trauma with significant blood loss (more than 500 mL) within the last 3 months prior to screening.
- Current treatment with systemic (oral or i.v.) corticosteroids, MAO inhibitors, nonselective beta-blockers, growth hormone, herbal products or non-routine vitamins. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months prior to screening.
- Significant history of alcoholism or drug/chemical abuse as per investigator's judgement or a positive result in the drug/alcohol screen at the screening visit.
- Smoker (defined as a subject who is smoking more than 5 cigarettes or the equivalent per day)
- Not able or willing to refrain from smoking and use of nicotine gum or transdermal nicotine patches during the inpatient period.
- Subject with mental incapacity or language barriers precluding adequate understanding or co-operation or who, in the opinion of the investigator, should not participate in the trial.
- Potentially non-compliant or uncooperative during the trial, as judged by the investigator.
- Any condition that would interfere with trial participation or evaluation of results, as judged by the investigator.
- Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods (adequate contraceptive methods include sterilisation, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner).
- Use of drugs, which may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilisation, or recovery from hypoglycaemia
- Severe acute and/or chronic diseases
- Diseases of the skin which could interfere with application of the catheters as judged by the investigator
- Previous participation in this trial. Participation is defined as randomised.
- Receipt of any investigational medicinal product within 3 months before randomisation in this trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open, Non-randomized, Single-center Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemic Clamp in Type 1 Diabetes Mellitus Subjects
Primary objective is to investigate the feasibility and stability of determining the endogenous glucose production during a hypoglycaemic clamp in type 1 diabetes mellitus subjects by a stable tracer to tracee ratio with an enrichment of 4% and a variation below +/-30%.
Population: twenty type 1 diabetic subjects
Study design: Single-center, open, non- randomized, pilot-study
Read the detailed description
Each subject will participate on 3 Visits. The total study duration for each subject will be approximately one month.The trial can be divided into:
- Screening Visit (Visit 1)
- Hypoglycaemic clamp Visit (Visit 2)
- Follow up Visit (Visit 3)
Screening Visit (Visit1):
The subject will be asked to attend the screening visit fasting. The following data will be assessed and performed: informed consent signed and dated, inclusion and exclusion criteria for the study, a full medical history including current medication, physical examination and laboratory examination of blood/urine samples. For women in childbearing potential a urine pregnancy test will be performed.
Hypoglycaemic Visit (Visit2):
Each subject will be asked to attend the clinical unit at approximately 20:00 in the evening on day 1. Thereafter the subject will receive an insulin and glucose infusion intravenously in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately 08:00 in the morning of day 2. At 05:00 hours D-[6,6-2H2] glucose (100 g/l) solution will be given i.v. as a primed (9.6 mg/kg/min) for one minute and a constant (0.08 mg/kg/min) infusion until the last blood sampling of the plasma glucose level of 4.0 mmol/L will be performed.
At 08:00 hours in the morning at day 2, insulin infusion will be increased to 1.5 mU/kg/min for each subject and the Plasma Glucose will be kept at a plateau of 5.5 mmol/L by a controlled variable intravenous infusion of glucose (10% glucose enriched with 4mg [6,6-2H2] glucose /ml) for one hour. Afterwards, plasma glucose is allowed to fall to a plateau of 3.5 mmol/L, then to a nadir of 2.5 mmol/L, then to a blood glucose level of 4.0 mmol/L and finally back to a level of 5.5 mmol/L for safety reasons. Blood sampling for measurement of plasma glucose, [6,6-2H2] glucose (labelled glucose),glucagon, vital signs, hypoglycaemic symptoms questionnaire and hypoglycaemic awareness will be performed at each plasma glucose plateau. The subject will be discharged from the clinic at day 2, or later if deemed necessary by the investigator.
Follow up Visit (Visit 3):
The subject will attend the Visit 3, 3 - 10 days after Visit 2. The following data will be assessed and performed: concomitant medication, including current diabetes treatment, adverse events, a full physical examination and laboratory examination of blood/urine samples. For women in childbearing potential a urine pregnancy test will be performed.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Insulin human
- Keywords
- Endogenous glucose production, Type 1 diabetes mellitus, hypoglycaemic clamp, tracer to technique, pharmacodynamics, pharmacokinetics
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin humanDrug
Also called Actrapid
Induces hypoglycaemia
| Study group | Role | What they receive |
|---|---|---|
| Insulin human (Actrapid) | Experimental | At 22:00 subject will receive insulin human (Actrapid) intravenously in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately 08:00 in the morning of day 2. At 8:00 am, in the morning at day 2, human insulin infusion will be increased to 1.5 mU/kg/min for each subject until approx. 12 pm for hypoglycaemia induction. Receives: Drug: Insulin human |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tracer to Tracee Ratio (the absolute relative difference ARDi )
Measured: 8 hours
Secondary outcomes (1)
Tracer to tracee Ratio
For each subject, the mean absolute relative difference (MARD) of the tracer to tracee ratio (4% enrichment) during variable Glucose Infusion Rate from the begin of the experiment until the end of the hypoglycaemic clamp.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionMar 2016
- Study completionMar 2016
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 Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Medical University of GrazThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pieber Thomas, MD, Medical University of Graz
- Investigators
- Thomas R. Pieber, MD, Principal investigator, Medical University of Graz, Internal Medicine, Endocrinology and Metabolism
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02028078
- Sponsor's protocol ID
- PILOT_EGP
- Acronym
- PILOT_EGP
- Status last verified
- Sep 2016
- First submitted
- 3 Jan 2014
- Last updated
- 12 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Zenz S, Mader JK, Regittnig W, Brunner M, Korsatko S, Boulgaropoulos B, Magnes C, Raml R, Narath SH, Eller P, Augustin T, Pieber TR. Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycemia in T1DM. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1408-1417. doi: 10.1210/jc.2017-01836.
PubMed 29408994
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Non-randomized, Single-center Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemic Clamp in Type 1 Diabetes Mellitus Subjects
- ClinicalTrials.gov ID
- NCT02028078
- Acronym / sponsor ID
- PILOT_EGP / PILOT_EGP
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Endogenous glucose production, Type 1 diabetes mellitus, hypoglycaemic clamp, tracer to technique, pharmacodynamics, pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 6 Jan 2014 (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.
Primary objective is to investigate the feasibility and stability of determining the endogenous glucose production during a hypoglycaemic clamp in type 1 diabetes mellitus subjects by a stable tracer to tracee ratio with an enrichment of 4% and a variation below +/-30%.
Population: twenty type 1 diabetic subjects
Study design: Single-center, open, non- randomized, pilot-study
Detailed description
Each subject will participate on 3 Visits. The total study duration for each subject will be approximately one month.The trial can be divided into:
- Screening Visit (Visit 1)
- Hypoglycaemic clamp Visit (Visit 2)
- Follow up Visit (Visit 3)
Screening Visit (Visit1):
The subject will be asked to attend the screening visit fasting. The following data will be assessed and performed: informed consent signed and dated, inclusion and exclusion criteria for the study, a full medical history including current medication, physical examination and laboratory examination of blood/urine samples. For women in childbearing potential a urine pregnancy test will be performed.
Hypoglycaemic Visit (Visit2):
Each subject will be asked to attend the clinical unit at approximately 20:00 in the evening on day 1. Thereafter the subject will receive an insulin and glucose infusion intravenously in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately 08:00 in the morning of day 2. At 05:00 hours D-[6,6-2H2] glucose (100 g/l) solution will be given i.v. as a primed (9.6 mg/kg/min) for one minute and a constant (0.08 mg/kg/min) infusion until the last blood sampling of the plasma glucose level of 4.0 mmol/L will be performed.
At 08:00 hours in the morning at day 2, insulin infusion will be increased to 1.5 mU/kg/min for each subject and the Plasma Glucose will be kept at a plateau of 5.5 mmol/L by a controlled variable intravenous infusion of glucose (10% glucose enriched with 4mg [6,6-2H2] glucose /ml) for one hour. Afterwards, plasma glucose is allowed to fall to a plateau of 3.5 mmol/L, then to a nadir of 2.5 mmol/L, then to a blood glucose level of 4.0 mmol/L and finally back to a level of 5.5 mmol/L for safety reasons. Blood sampling for measurement of plasma glucose, [6,6-2H2] glucose (labelled glucose),glucagon, vital signs, hypoglycaemic symptoms questionnaire and hypoglycaemic awareness will be performed at each plasma glucose plateau. The subject will be discharged from the clinic at day 2, or later if deemed necessary by the investigator.
Follow up Visit (Visit 3):
The subject will attend the Visit 3, 3 - 10 days after Visit 2. The following data will be assessed and performed: concomitant medication, including current diabetes treatment, adverse events, a full physical examination and laboratory examination of blood/urine samples. For women in childbearing potential a urine pregnancy test will be performed.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Insulin human (Actrapid) | Experimental | Drug: Insulin humanAt 22:00 subject will receive insulin human (Actrapid) intravenously in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately 08:00 in the morning of day 2. At 8:00 am, in the morning at day 2, human insulin infusion will be increased to 1.5 mU/kg/min for each subject until approx. 12 pm for hypoglycaemia induction. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 1.)Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- 2. )Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months prior to screening visit 3.)Male or female, aged 18 - 64 years (both inclusive) 4.) Body mass index (BMI) 18.0 - 28.0 kg/m2 (both inclusive) 5.) HbA1c 42 - 80 mmol/mol (6.0-9.5%) 6. )Treated with daily insulin injections or continuous s.c. insulin infusion (CSII) ≥ 12 months. Stable insulin dose as judged by the investigator.
Key exclusion criteria (32 listed)
- Known or suspected hypersensitivity to trial product(s) or related products
- Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) as judged by the investigator
- Severe hypoglycaemia within 1 month of screening
- Hypoglycaemia unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
- Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the investigator and any of the following laboratory safety results:
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: ActrapidInduces hypoglycaemia | Drug | Insulin human (Actrapid) |
Primary outcome
Tracer to Tracee Ratio (the absolute relative difference ARDi )
Time frame: 8 hours
1 secondary outcome
Tracer to tracee Ratio
Time frame: 8 hours
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 12 Sep 2016.
- Derived from this study: PubMed 29408994Zenz S, Mader JK, Regittnig W, Brunner M, Korsatko S, Boulgaropoulos B, Magnes C, Raml R, Narath SH, Eller P, Augustin T, Pieber TR. Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycemia in T1DM. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1408-1417. doi: 10.1210/jc.2017-01836.
- Medical University of GrazLink provided by the sponsor.
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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.
Thomas R. Pieber, MD principal investigator
Medical University of Graz, Internal Medicine, Endocrinology and Metabolism
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Insulin human in people with Type 1 Diabetes Mellitus, run by Medical University of Graz at 1 site in Austria.
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 2 inclusion and 32 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 12 Sep 2016. 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 Austria. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Tracer to Tracee Ratio (the absolute relative difference ARDi ) (time frame: 8 hours). 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 NCT02028078, 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 12 Sep 2016.