Type 1 Diabetes MellitusNCT03547427
Glucagon Counterregulation in Type 1 Diabetes
A study testing Basal insulin alone, Basal pramlintide and reduced basal insulin and CGM in people with Type 1 Diabetes Mellitus, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to find out whether the combination of insulin and pramlintide is better than insulin alone at helping the pancreas release glucagon in response to a low blood sugar episode. A secondary goal is to assess whether basal pramlintide will delay gastric emptying. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Basal insulin alone, Basal pramlintide and reduced basal insulin and CGM
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2018to 11 Mar 2019
- 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 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 5 years and using insulin for at least 5 years
- Use of an insulin pump for at least 6 months with established parameters for basal rate(s), carbohydrate ratio(s) and insulin sensitivity factor(s) for at least 3 months.
- HbA1c level <10.5% at screening
- Demonstration of proper mental status and cognition for the study
- Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol
Who cannot join
- Admission for diabetic ketoacidosis in the 6 months prior to enrollment.
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 3 months prior to enrollment.
- Hematocrit less that the lower limit of normal for the assay.
- Pregnancy, breast-feeding, or intention of becoming pregnant over time of study procedures
- A known medical condition, which in the opinion of the investigator or designee, would put the participant or study at risk
- A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol
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- Current use of some drugs and supplements
- Participation in another pharmaceutical or device trial at the time of enrollment or during the study
- Basal insulin rates less than 0.01 units per hour
- Diagnosed food allergies that would prohibit the consumption of a standardized meal
- Any reason the study MD considers that the subject is not appropriate for the trial
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Center for Diabetes Technology
Charlottesville, Virginia, 22903
About this study
Official title: Enhancement of Glucagon Counterregulation in Type 1 Diabetes by Basal Amylin Replacement
The purpose of this study is to find out whether the combination of insulin and pramlintide is better than insulin alone at helping the pancreas release glucagon in response to a low blood sugar episode.
A secondary goal is to assess whether basal pramlintide will delay gastric emptying.
Read the detailed description
Participation in this study will require three (3) study visits over 12 weeks: one screening visit lasting 2-3 hours, and two overnight study visits at the university's Clinical Research Unit (CRU). The two overnight visits will last about 22 hours.
During the CRU admission, all subjects will wear a Continuous Glucose Monitor (CGM) starting 2-3 days prior to the CRU admission and after having a CGM training.
Eligible subjects will be randomized to either insulin- or exercise-induced hypoglycemia group. Each subject will have two overnight CRU admissions in randomized order: Experimental (basal pramlintide + 25% reduction of basal insulin) or Control (standard basal insulin therapy) admissions. During these two admissions, the study team will deliberately induce hypoglycemia as follows:
Subjects randomized to insulin-induced hypoglycemia admission will receive an insulin bolus(s) dosed to reach blood sugar of less than 55 mg/dL.
Subjects randomized to exercise-induced hypoglycemia will participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.
After hypoglycemia induction, all subjects will receive one and the same standard meal (lunch) mixed with 1.5 g liquid acetaminophen to measure how quickly acetaminophen is absorbed to estimate the rate of gastric emptying.
The study team will collect blood samples during the hypoglycemic induction and the gastric emptying monitoring which will be analysed for levels of various substances used to address the study goals.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Basal insulin alone, Basal pramlintide and reduced basal insulin, CGM, Acetaminophen test, Insulin-induced hypoglycemia
- Keywords
- Type 1 Diabetes Mellitus, Pramlintide, Lispro Insulin, Continuous Glucose Monitor (CGM), Acetaminophen, Hypoglycemia, Exercise
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Basal insulin aloneOther
A study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at according to the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.
Basal pramlintide and reduced basal insulinOther
A study insulin pump containing pramlintide will be programmed to deliver pramlintide at 6:1 pramlintide:insulin ratio. Simultaneously, a study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at ~25% reduced rate from the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.
CGMOther
Subjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions.
Acetaminophen testOther
Consumption of a standardized meal mixed with added 1.5 g liquid acetaminophen
Insulin-induced hypoglycemiaOther
During insulin-induced hypoglycemia admission, subjects will receive an insulin bolus(s) dosed to reach blood sugar of less than 55 mg/dL.
Exercise-induced hypoglycemiaOther
During exercise-induced hypoglycemia admission, subjects participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.
| Study group | Role | What they receive |
|---|---|---|
| Insulin hypoglycemia + pramlintide | Experimental | Subjects will have a 25% reduction in their standard basal insulin therapy with concurrent basal pramlintide infusion ('Basal pramlintide and reduced basal insulin'). They will receive a Lispro bolus to induce hypoglycemia of ≤55mg/dL ('Insulin-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. Receives: Other: Basal pramlintide and reduced basal insulin; Other: CGM; Other: Acetaminophen test; Other: Insulin-induced hypoglycemia |
| Insulin hypoglycemia | Active comparator | Subjects will have their standard basal insulin treatment ('Basal insulin alone') and receive a Lispro bolus to induce hypoglycemia of ≤55mg/dL ('Insulin-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. Receives: Other: Basal insulin alone; Other: CGM; Other: Acetaminophen test; Other: Insulin-induced hypoglycemia |
| Exercise hypoglycemia + pramlintide | Experimental | Subjects will have a 25% reduction in their standard basal insulin therapy with concurrent basal pramlintide infusion ('Basal pramlintide and reduced basal insulin'). They will have three bouts of exercise to induce hypoglycemia of ≤55mg/dL ('Exercise-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. Receives: Other: Basal pramlintide and reduced basal insulin; Other: CGM; Other: Acetaminophen test; Other: Exercise-induced hypoglycemia |
| Exercise hypoglycemia | Active comparator | Subjects will have their standard basal insulin treatment ('Basal insulin alone'). They will have three bouts of exercise to induce hypoglycemia of ≤55mg/dL ('Exercise-induced hypoglycemia' ). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. Receives: Other: Basal insulin alone; Other: CGM; Other: Acetaminophen test; Other: Exercise-induced hypoglycemia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative glucagon counterregulation (GCR) response
The primary outcome is the relative glucagon counterregulation (GCR) response, computed as the ratio between average glucagon concentration in response to insulin-induced hypoglycemia, and the pre-hypoglycemic baseline value. The baseline glucagon level is defined as the average concentration of glucagon when the falling plasma glucose is below 100mg/dl but above the hypoglycemic threshold of 60mg/dl. The response to hypoglycemia is the average concentration of glucagon between the hypoglycemic threshold crossing point and the time of the meal ingestion.
Measured: about 19 hours
Secondary outcomes (2)
Maximal glucagon counterregulation (GCR) response
The maximal glucagon concentration achieved during the response to hypoglycemia
Measured: about 19 hours
Rate of gastric emptying
The time to reaching ½ maximal acetaminophen concentration in the bloodstream after ingesting a meal mixed with 1.5 g of liquid acetaminophen.
Measured: about 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2018
- Study start20 May 2018
- Primary completion11 Mar 2019
- Study completion11 Mar 2019
Why it stopped: Clinical staffing issues and COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leon Farhi, PhD, University of Virginia
- Investigators
- Leon S. Farhy, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03547427
- Sponsor's protocol ID
- 20364
- Status last verified
- Mar 2022
- First submitted
- 24 May 2018
- Last updated
- 28 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: To be determined
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancement of Glucagon Counterregulation in Type 1 Diabetes by Basal Amylin Replacement
- ClinicalTrials.gov ID
- NCT03547427
- Acronym / sponsor ID
- 20364
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Type 1 Diabetes Mellitus, Pramlintide, Lispro Insulin, Continuous Glucose Monitor (CGM), Acetaminophen, Hypoglycemia, Exercise
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Clinical staffing issues and COVID-19 pandemic
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 20 May 2018 (actual)
- Primary completion
- 11 Mar 2019 (actual)
- Study completion
- 11 Mar 2019 (actual)
- First posted
- 6 Jun 2018 (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.
The purpose of this study is to find out whether the combination of insulin and pramlintide is better than insulin alone at helping the pancreas release glucagon in response to a low blood sugar episode.
A secondary goal is to assess whether basal pramlintide will delay gastric emptying.
Detailed description
Participation in this study will require three (3) study visits over 12 weeks: one screening visit lasting 2-3 hours, and two overnight study visits at the university's Clinical Research Unit (CRU). The two overnight visits will last about 22 hours.
During the CRU admission, all subjects will wear a Continuous Glucose Monitor (CGM) starting 2-3 days prior to the CRU admission and after having a CGM training.
Eligible subjects will be randomized to either insulin- or exercise-induced hypoglycemia group. Each subject will have two overnight CRU admissions in randomized order: Experimental (basal pramlintide + 25% reduction of basal insulin) or Control (standard basal insulin therapy) admissions. During these two admissions, the study team will deliberately induce hypoglycemia as follows:
Subjects randomized to insulin-induced hypoglycemia admission will receive an insulin bolus(s) dosed to reach blood sugar of less than 55 mg/dL.
Subjects randomized to exercise-induced hypoglycemia will participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.
After hypoglycemia induction, all subjects will receive one and the same standard meal (lunch) mixed with 1.5 g liquid acetaminophen to measure how quickly acetaminophen is absorbed to estimate the rate of gastric emptying.
The study team will collect blood samples during the hypoglycemic induction and the gastric emptying monitoring which will be analysed for levels of various substances used to address the study goals.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Insulin hypoglycemia + pramlintide | Experimental | Other: Basal pramlintide and reduced basal insulin, Other: CGM, Other: Acetaminophen test, Other: Insulin-induced hypoglycemiaSubjects will have a 25% reduction in their standard basal insulin therapy with concurrent basal pramlintide infusion ('Basal pramlintide and reduced basal insulin'). They will receive a Lispro bolus to induce hypoglycemia of ≤55mg/dL ('Insulin-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. |
| Insulin hypoglycemia | Active comparator | Other: Basal insulin alone, Other: CGM, Other: Acetaminophen test, Other: Insulin-induced hypoglycemiaSubjects will have their standard basal insulin treatment ('Basal insulin alone') and receive a Lispro bolus to induce hypoglycemia of ≤55mg/dL ('Insulin-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. |
| Exercise hypoglycemia + pramlintide | Experimental | Other: Basal pramlintide and reduced basal insulin, Other: CGM, Other: Acetaminophen test, Other: Exercise-induced hypoglycemiaSubjects will have a 25% reduction in their standard basal insulin therapy with concurrent basal pramlintide infusion ('Basal pramlintide and reduced basal insulin'). They will have three bouts of exercise to induce hypoglycemia of ≤55mg/dL ('Exercise-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. |
| Exercise hypoglycemia | Active comparator | Other: Basal insulin alone, Other: CGM, Other: Acetaminophen test, Other: Exercise-induced hypoglycemiaSubjects will have their standard basal insulin treatment ('Basal insulin alone'). They will have three bouts of exercise to induce hypoglycemia of ≤55mg/dL ('Exercise-induced hypoglycemia' ). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 5 years and using insulin for at least 5 years
- Use of an insulin pump for at least 6 months with established parameters for basal rate(s), carbohydrate ratio(s) and insulin sensitivity factor(s) for at least 3 months.
- HbA1c level <10.5% at screening
- Demonstration of proper mental status and cognition for the study
- Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol
Key exclusion criteria (11 listed)
- Admission for diabetic ketoacidosis in the 6 months prior to enrollment.
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 3 months prior to enrollment.
- Hematocrit less that the lower limit of normal for the assay.
- Pregnancy, breast-feeding, or intention of becoming pregnant over time of study procedures
- A known medical condition, which in the opinion of the investigator or designee, would put the participant or study at risk
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 |
|---|---|---|
| Basal insulin aloneA study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at according to the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters. | Other | Exercise hypoglycemia, Insulin hypoglycemia |
| Basal pramlintide and reduced basal insulinA study insulin pump containing pramlintide will be programmed to deliver pramlintide at 6:1 pramlintide:insulin ratio. Simultaneously, a study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at ~25% reduced rate from the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters. | Other | Exercise hypoglycemia + pramlintide, Insulin hypoglycemia + pramlintide |
| CGMSubjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions. | Other | Exercise hypoglycemia, Exercise hypoglycemia + pramlintide, Insulin hypoglycemia, Insulin hypoglycemia + pramlintide |
| Acetaminophen testConsumption of a standardized meal mixed with added 1.5 g liquid acetaminophen | Other | Exercise hypoglycemia, Exercise hypoglycemia + pramlintide, Insulin hypoglycemia, Insulin hypoglycemia + pramlintide |
| Insulin-induced hypoglycemiaDuring insulin-induced hypoglycemia admission, subjects will receive an insulin bolus(s) dosed to reach blood sugar of less than 55 mg/dL. | Other | Insulin hypoglycemia, Insulin hypoglycemia + pramlintide |
| Exercise-induced hypoglycemiaDuring exercise-induced hypoglycemia admission, subjects participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL. | Other | Exercise hypoglycemia, Exercise hypoglycemia + pramlintide |
Primary outcome
Relative glucagon counterregulation (GCR) response
Time frame: about 19 hours
The primary outcome is the relative glucagon counterregulation (GCR) response, computed as the ratio between average glucagon concentration in response to insulin-induced hypoglycemia, and the pre-hypoglycemic baseline value. The baseline glucagon level is defined as the average concentration of glucagon when the falling plasma glucose is below 100mg/dl but above the hypoglycemic threshold of 60mg/dl. The response to hypoglycemia is the average concentration of glucagon between the hypoglycemic threshold crossing point and the time of the meal ingestion.
2 secondary outcomes
Maximal glucagon counterregulation (GCR) response
Time frame: about 19 hours
Rate of gastric emptying
Time frame: about 4 hours
Results and safety
The study was stopped early (reason given: Clinical staffing issues and COVID-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2022.
- Individual participant dataSharing planned: Yes. To be determined
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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.
Leon S. Farhy, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Basal insulin alone, Basal pramlintide and reduced basal insulin and CGM in people with Type 1 Diabetes Mellitus, run by University of Virginia 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 5 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: stopped early, as of the sponsor's last update on 28 Mar 2022. 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?
The study was stopped early (reason given: Clinical staffing issues and COVID-19 pandemic). 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?
Relative glucagon counterregulation (GCR) response (time frame: about 19 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2022.