Type 1 Diabetes MellitusNCT01986231
Safety Study of Repeated Doses of Glucagon on Animal Starch in the Liver
A study testing Glucagon in people with Type 1 Diabetes Mellitus, run by Legacy Health System at 1 site in United States.
Trial summary
The purpose of this study is to learn if giving multiple doses of a hormone called glucagon can cause a major decrease in liver glycogen (animal starch). Glucagon is currently approved by the Food and Drug Administration to be given as a large dose to treat severe low blood sugar. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Dec 2012
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes mellitus diagnosed for at least 6 months
- Current usage of subcutaneous insulin pump treatment
- Age 18-65 years
- HbA1c of 5.5 - 7.7% at screening visit
- BMI 18-35 kg/m2
- Willingness to follow all study procedures, including attending all clinic visits
- Willingness to sign informed consent and HIPAA documents
Who cannot join
- Pregnancy or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test.
- Renal insufficiency (serum creatinine of 2.0 mg/dL or greater).
- Serum ALT or AST equal to or greater than 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as a serum albumin of less than 3.3 g/dL; or serum bilirubin of over 2.
- Hematocrit of less than or equal to 34%.
- Congestive heart failure, NYHA class II, III or IV.
- Coronary artery or cerebrovascular disease.
Show all 19Show fewer
- Active foot ulceration.
- Active alcohol abuse, substance abuse, or severe mental illness (as judged by the principal investigator).
- Active malignancy, except basal cell or squamous cell skin cancers.
- Major surgical operation within 30 days prior to screening.
- Seizure disorder (epilepsy).
- Contraindication to an MRI scan, including having metallic splinters in the eye, a cardiac pacemaker, defibrillator, or any other ferromagnetic or electronically charged implanted device, or ferromagnetic clip(s) in the central nervous system.
- Currently administration of oral or parenteral corticosteroids.
- Use of an investigational drug within 30 days prior to screening.
- Bleeding disorder, treatment with warfarin, or platelet count below 50,000.
- History weight loss of ≥ 5 lbs over the prior month.
- Weight ≥ 300 lbs.
- Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen.
- Any reason the principal investigator deems exclusionary.
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health and Science University
Portland, Oregon, 97239
About this study
Official title: The Effect of Repeated Doses of Subcutaneous Glucagon on Hepatic Glycogen Stores in Persons With Type 1 Diabetes
The purpose of this study is to learn if giving multiple doses of a hormone called glucagon can cause a major decrease in liver glycogen (animal starch). Glucagon is currently approved by the Food and Drug Administration to be given as a large dose to treat severe low blood sugar. Our group is studying whether glucagon can be given in repeated small doses to prevent hypoglycemia.
Read the detailed description
Hypoglycemia remains a barrier to optimal glucose control, which is necessary to prevent diabetes-related complications including eye, kidney, and nerve diseases. Despite treatment advances such as insulin pump therapy and continuous glucose monitoring, hypoglycemia remains a concern, even when insulin is given in a closed-loop system. A closed-loop system consists of a glucose-measuring device, from which data are collected and entered into an algorithm, which in turn controls insulin delivery. The difficulty of delivering regular or analog insulin in such a manner is related to its slow onset and prolonged effect when delivered subcutaneously. Until a more rapidly-acting insulin preparation is available, discontinuation of subcutaneous insulin during impending hypoglycemia, with any algorithm, may be insufficient to prevent hypoglycemia.
Glucagon, a hormone secreted from the alpha cells of the normal endocrine pancreas, rapidly raises circulating glucose levels within minutes via glycogenolysis, even when given subcu-taneously. Glucagon is approved for use as a parenteral injection for treatment of severe hypoglycemia. Our group has successfully completed studies in humans using a closed-loop system that delivers insulin (in a nearly continuous fashion) to prevent and treat hyperglycemia as well as glucagon (intermittently) to prevent and treat hypoglycemia.
However, it is unknown whether or not repeated doses lead to hepatic glycogen depletion, which would increase the risk of a severe hypoglycemic episode. 13C MRS (magnetic resonance spectroscopy) has been successfully used to quantify hepatic glycogen in a non-invasive fashion. We are proposing to use 13C MRS to compare glycogen stores in subjects with type 1 diabetes after a period without glucagon vs after a period of repeated glucagon dosing. The comparisons will be made when glycogen stores should be replete (after a lunch meal) and when glycogen stores should be lower (after an overnight fast). If repeated doses of glucagon do cause glycogen depletion, then we would revise our dosing strategy in the closed-loop system and/or consider alternative methods for preventing hypoglycemia.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Glucagon
- Keywords
- diabetes, insulin, glucagon, glycogen, MRS
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonDrug
Also called GlucaGen
Subjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg. Glucagon will be reconstituted immediately prior to administration and each dose will be administered subcutaneously via syringe/needle. The first glucagon dose is at hour 17, second at hour 22, third at hour 24, fourth at hour 27, fifth at hour 29, sixth at hour 31, seventh at hour 33, eighth at hour 35.
| Study group | Role | What they receive |
|---|---|---|
| Open-Label Glucagon | Experimental | Subjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg. Receives: Drug: Glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess Difference in Hepatic Glycogen Measured in the Fasting State Before vs. After Repeated Glucagon Administration
The mean difference in estimated hepatic glycogen will be assessed using Carbon 13 Magnetic Resonance Spectroscopy before vs. after glucagon administration in the fasting state.
Measured: Baseline and 41 hours
Secondary outcomes (1)
Assess Difference in Hepatic Glycogen Measured in the Fed State Before vs. After Repeated Glucagon Administration
The mean difference in estimated hepatic glycogen will be assessed using Carbon 13 Magnetic Resonance Spectroscopy before vs. after glucagon administration in the fed state.
Measured: Baseline and 41 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2013 (estimated)
- Study startJan 2011
- Primary completionDec 2012
- Study completionDec 2012
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 Type 1 Diabetes MellitusStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Legacy Health System
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, Oregon Health and Science University
- Responsible party
- Principal investigator, W. Kenneth Ward, Legacy Health System
- Investigators
- W Kenneth Ward, MD, Principal investigator, Legacy Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01986231
- Sponsor's protocol ID
- IRB00006947
- Status last verified
- Apr 2015
- First submitted
- 5 Nov 2013
- Last updated
- 4 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Castle JR, El Youssef J, Bakhtiani PA, Cai Y, Stobbe JM, Branigan D, Ramsey K, Jacobs P, Reddy R, Woods M, Ward WK. Effect of Repeated Glucagon Doses on Hepatic Glycogen in Type 1 Diabetes: Implications for a Bihormonal Closed-Loop System. Diabetes Care. 2015 Nov;38(11):2115-9. doi: 10.2337/dc15-0754. Epub 2015 Sep 4.
PubMed 26341131
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Repeated Doses of Subcutaneous Glucagon on Hepatic Glycogen Stores in Persons With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01986231
- Acronym / sponsor ID
- IRB00006947
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- diabetes, insulin, glucagon, glycogen, MRS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Legacy Health SystemUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, Oregon Health and Science University
- Study start
- Jan 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 18 Nov 2013 (estimated)
- Results
- Posted 30 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn if giving multiple doses of a hormone called glucagon can cause a major decrease in liver glycogen (animal starch). Glucagon is currently approved by the Food and Drug Administration to be given as a large dose to treat severe low blood sugar. Our group is studying whether glucagon can be given in repeated small doses to prevent hypoglycemia.
Detailed description
Hypoglycemia remains a barrier to optimal glucose control, which is necessary to prevent diabetes-related complications including eye, kidney, and nerve diseases. Despite treatment advances such as insulin pump therapy and continuous glucose monitoring, hypoglycemia remains a concern, even when insulin is given in a closed-loop system. A closed-loop system consists of a glucose-measuring device, from which data are collected and entered into an algorithm, which in turn controls insulin delivery. The difficulty of delivering regular or analog insulin in such a manner is related to its slow onset and prolonged effect when delivered subcutaneously. Until a more rapidly-acting insulin preparation is available, discontinuation of subcutaneous insulin during impending hypoglycemia, with any algorithm, may be insufficient to prevent hypoglycemia.
Glucagon, a hormone secreted from the alpha cells of the normal endocrine pancreas, rapidly raises circulating glucose levels within minutes via glycogenolysis, even when given subcu-taneously. Glucagon is approved for use as a parenteral injection for treatment of severe hypoglycemia. Our group has successfully completed studies in humans using a closed-loop system that delivers insulin (in a nearly continuous fashion) to prevent and treat hyperglycemia as well as glucagon (intermittently) to prevent and treat hypoglycemia.
However, it is unknown whether or not repeated doses lead to hepatic glycogen depletion, which would increase the risk of a severe hypoglycemic episode. 13C MRS (magnetic resonance spectroscopy) has been successfully used to quantify hepatic glycogen in a non-invasive fashion. We are proposing to use 13C MRS to compare glycogen stores in subjects with type 1 diabetes after a period without glucagon vs after a period of repeated glucagon dosing. The comparisons will be made when glycogen stores should be replete (after a lunch meal) and when glycogen stores should be lower (after an overnight fast). If repeated doses of glucagon do cause glycogen depletion, then we would revise our dosing strategy in the closed-loop system and/or consider alternative methods for preventing hypoglycemia.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-Label Glucagon | Experimental | Drug: GlucagonSubjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Type 1 diabetes mellitus diagnosed for at least 6 months
- Current usage of subcutaneous insulin pump treatment
- Age 18-65 years
- HbA1c of 5.5 - 7.7% at screening visit
- BMI 18-35 kg/m2
Key exclusion criteria (19 listed)
- Pregnancy or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test.
- Renal insufficiency (serum creatinine of 2.0 mg/dL or greater).
- Serum ALT or AST equal to or greater than 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as a serum albumin of less than 3.3 g/dL; or serum bilirubin of over 2.
- Hematocrit of less than or equal to 34%.
- Congestive heart failure, NYHA class II, III or IV.
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 |
|---|---|---|
| GlucagonAlso: GlucaGenSubjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg. Glucagon will be reconstituted immediately prior to administration and each dose will be administered subcutaneously via syringe/needle. The first glucagon dose is at hour 17, second at hour 22, third at hour 24, fourth at hour 27, fifth at hour 29, sixth at hour 31, seventh at hour 33, eighth at hour 35. | Drug | Open-Label Glucagon |
Primary outcome
Assess Difference in Hepatic Glycogen Measured in the Fasting State Before vs. After Repeated Glucagon Administration
Time frame: Baseline and 41 hours
The mean difference in estimated hepatic glycogen will be assessed using Carbon 13 Magnetic Resonance Spectroscopy before vs. after glucagon administration in the fasting state.
1 secondary outcome
Assess Difference in Hepatic Glycogen Measured in the Fed State Before vs. After Repeated Glucagon Administration
Time frame: Baseline and 41 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26341131Castle JR, El Youssef J, Bakhtiani PA, Cai Y, Stobbe JM, Branigan D, Ramsey K, Jacobs P, Reddy R, Woods M, Ward WK. Effect of Repeated Glucagon Doses on Hepatic Glycogen in Type 1 Diabetes: Implications for a Bihormonal Closed-Loop System. Diabetes Care. 2015 Nov;38(11):2115-9. doi: 10.2337/dc15-0754. Epub 2015 Sep 4.
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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.
W Kenneth Ward, MD principal investigator
Legacy Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucagon in people with Type 1 Diabetes Mellitus, run by Legacy Health System at 1 site in United States.
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 19 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 4 May 2015. 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 United States. 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 30 Apr 2015). 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?
Assess Difference in Hepatic Glycogen Measured in the Fasting State Before vs. After Repeated Glucagon Administration (time frame: Baseline and 41 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 NCT01986231, 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 4 May 2015.