Type 1 Diabetes MellitusALM002NCT01434862
Pramlintide Combined With Model Predictive Control Algorithm
A study testing Closed loop with pramlintide, Closed loop without pramlintide and Open loop with pramlintide in people with Type 1 Diabetes Mellitus, run by University of Virginia at 1 site in United States.
Trial summary
This is a scientific research study that will look at how a "closed-loop" system and the drug Pramlintide may work together to improve blood sugar control in people with type 1 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Closed loop with pramlintide, Closed loop without pramlintide and Open loop with pramlintide
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Feb 2012
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least six months (the diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determination are not needed).
- Age 21 to 65 years
- For females, not currently known to be pregnant
- An understanding of the protocol and a willingness to follow it
- HbA1c between 7 and 9%
- Normal renal function (determined utilizing the comprehensive metabolic panel at screening with the Modification of Diet in Renal Disease (MDRD) formula and defined by estimated Glomerular Filtration Rate (eGFR) of ≥60 ml/min/1.73 m2.
- Hematocrit >36 (females); >38 (males)
Who cannot join
- Known hypersensitivity to SYMLIN or any of its components, including metacresol
- Poor compliance with current insulin regimen
- Poor compliance with prescribed self-blood glucose monitoring
- HbA1c <7 or >9%
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 2 weeks prior to enrollment
- Active infection
Show all 35Show fewer
- Current use of dietary supplements (subjects may be enrolled if they stop taking dietary supplements two weeks prior to admission and for the duration of their participation)
- Active gastroparesis
- Use of drugs that stimulate gastrointestinal motility (e.g. metoclopramide)
- Diabetic ketoacidosis in the past 3 months
- Current treatment for a seizure disorder
- Cystic fibrosis
- Asthma requiring hospitalization or treatment with oral steroids within the past year
- Presence of a uncontrolled adrenal disorder
- A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:
- Inpatient psychiatric treatment in the past 6 months
- Abnormal liver function (Transaminase >2 times the upper limit of normal)
- Heart failure
- Coronary artery disease
- Arrhythmia
- Seizure disorder
- Any carcinogenic disease
- Creatinine concentration above the upper limit of normal for age and sex
- Active coronary artery disease
- Uncontrolled thyroid disease
- Use or abuse of alcohol
- Active kidney dialysis
- If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
- Note: adequately treated thyroid disease and celiac disease do not exclude subjects from enrollment
- Addison's disease
- Current use of a beta blocker medication
- Hematocrit < 36 (female), <38 (male)
- Current use of oral glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study
- Allergy to the sensor or to one of its components
- Continued use of acetaminophen.
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
This is a scientific research study that will look at how a "closed-loop" system and the drug Pramlintide may work together to improve blood sugar control in people with type 1 diabetes mellitus. Pramlintide is approved by the Food and Drug Administration (FDA) and is given as an injection (subcutaneous) that works with insulin to lower blood sugar.
Read the detailed description
The objective of this study is to test whether standard pramlintide treatment plus a closed-loop insulin therapy is more efficacious in controlling glycemia than either of the individual therapies. The control algorithm is in effect an insulin dose calculator for mimicry of basal insulin secretion by estimating requirements for basal rates of insulin pump infusion based on current and past glucose levels estimated from the Continuous Glucose Monitor (CGM) device and prior insulin infusions. The closed-loop system-recommended insulin will replace (in a clinical setting) the basal rate insulin that the patient would normally use. The patients' meal insulin needs will be estimated using an insulin-to-carbohydrate ratio as per standard clinical practice and will be optimized prior to admission to the Clinical Research Unit.
The primary goal of this feasibility study is to test the hypothesis that the combination of a closed loop system (Open-Loop Informed with a Model Predicted Control (MPC) algorithm plus a safety system module (SSM)) with pramlintide (a synthetic analog of the hormone amylin which in health is released by the β-cells along with insulin) treatment will improve glucose control versus each of the individual therapies. Because pramlintide reduces hyperglycemia extremes generated at meals and closed loop control markedly reduces the risk of hypoglycemia, thus representing potentially important complementary actions to reduced variability - the investigators expect to find decreased hyperglycemia while simultaneously decreasing hypoglycemia risks.
Secondary goals are to explore factors associated with achieving safer and/or more effective closed loop control. For example, based upon our work in animal models, one secondary goal is to explore whether moderate inhibition of α-cell glucagon, known to occur with pramlintide administration in the early postprandial period, has the potential to repair inadequate glucagon counterregulation.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Closed loop with pramlintide, Closed loop without pramlintide, Open loop with pramlintide
- Keywords
- Type 1 Diabetes Mellitus
- 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.
Closed loop with pramlintideDrug
Dose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily.
Closed loop without pramlintideDevice
This visit will assess how well the closed loop system works without the pramlintide.
Open loop with pramlintideDrug
Dose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily.
| Study group | Role | What they receive |
|---|---|---|
| Closed loop with pramlintide | Experimental | Pramlintide will be provided to study subjects who will subsequently be admitted for inpatient testing with the closed loop system. The term closed loop refers to insulin adjustment automatically regulated by computer input to the insulin pump based on monitoring (often a combination of patient blood glucose (BG) testing and/or continuous glucose monitoring (CGM)). Receives: Drug: Closed loop with pramlintide |
| Closed loop without pramlintide | Experimental | This visit is necessary to assess how well the closed loop system works without the pramlintide (how well it protects from hypoglycemia and hyperglycemia). It will be the exact protocol as for the closed loop with pramlintide but without the medication. Receives: Device: Closed loop without pramlintide |
| Open loop with pramlintide | Experimental | The term open loop refers to insulin infusions regulated in their delivery based on patient self-monitoring and adjustment. The study subject will be in charge of their insulin treatment while also receiving pramlintide. Receives: Drug: Open loop with pramlintide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Blood glucose tests within target range of 70 to 180 mg/dl
Percent of Blood glucose tests within target range of 70 to 180 mg/dl
The primary outcome variable of glucose control within an American Diabetes Association (ADA) standard target range between 70 mg/dl to 180 mg/dl on a Yellow Springs Instrument (YSI) glucose analyzer. This is based upon the sample size estimate difference expected for % time within target range between artificial pancreas vs. patient control vs. Pramlintide plus artificial pancreas.
Measured: 24 hours
Secondary outcomes (1)
Percent of Continuous Glucose Monitoring (CGM) System estimated blood glucose within target range of 70 to 180 mg/dl
A secondary analysis will be performed using the Continuous Glucose Monitoring [CGM] data estimated blood glucose within the American Diabetes Association [ADA] recommended target of 70-180 mg/dl.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2011 (estimated)
- Study startFeb 2011
- Primary completionFeb 2012
- Study completionFeb 2012
Why it stopped: Modified study; created new study as a result of these modifications
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- The Paul Manning Foundation
- Responsible party
- Principal investigator, Anthony McCall, University of Virginia
- Investigators
- Anthony McCall, M.D., Ph.D., Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434862
- Sponsor's protocol ID
- 15401
- Acronym
- ALM002
- Status last verified
- Apr 2014
- First submitted
- 7 Sep 2011
- Last updated
- 1 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pramlintide Combined With Model Predictive Control Algorithm
- ClinicalTrials.gov ID
- NCT01434862
- Acronym / sponsor ID
- ALM002 / 15401
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Type 1 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Modified study; created new study as a result of these modifications
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- The Paul Manning Foundation
- Study start
- Feb 2011
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 15 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a scientific research study that will look at how a "closed-loop" system and the drug Pramlintide may work together to improve blood sugar control in people with type 1 diabetes mellitus. Pramlintide is approved by the Food and Drug Administration (FDA) and is given as an injection (subcutaneous) that works with insulin to lower blood sugar.
Detailed description
The objective of this study is to test whether standard pramlintide treatment plus a closed-loop insulin therapy is more efficacious in controlling glycemia than either of the individual therapies. The control algorithm is in effect an insulin dose calculator for mimicry of basal insulin secretion by estimating requirements for basal rates of insulin pump infusion based on current and past glucose levels estimated from the Continuous Glucose Monitor (CGM) device and prior insulin infusions. The closed-loop system-recommended insulin will replace (in a clinical setting) the basal rate insulin that the patient would normally use. The patients' meal insulin needs will be estimated using an insulin-to-carbohydrate ratio as per standard clinical practice and will be optimized prior to admission to the Clinical Research Unit.
The primary goal of this feasibility study is to test the hypothesis that the combination of a closed loop system (Open-Loop Informed with a Model Predicted Control (MPC) algorithm plus a safety system module (SSM)) with pramlintide (a synthetic analog of the hormone amylin which in health is released by the β-cells along with insulin) treatment will improve glucose control versus each of the individual therapies. Because pramlintide reduces hyperglycemia extremes generated at meals and closed loop control markedly reduces the risk of hypoglycemia, thus representing potentially important complementary actions to reduced variability - the investigators expect to find decreased hyperglycemia while simultaneously decreasing hypoglycemia risks.
Secondary goals are to explore factors associated with achieving safer and/or more effective closed loop control. For example, based upon our work in animal models, one secondary goal is to explore whether moderate inhibition of α-cell glucagon, known to occur with pramlintide administration in the early postprandial period, has the potential to repair inadequate glucagon counterregulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Closed loop with pramlintide | Experimental | Drug: Closed loop with pramlintidePramlintide will be provided to study subjects who will subsequently be admitted for inpatient testing with the closed loop system. The term closed loop refers to insulin adjustment automatically regulated by computer input to the insulin pump based on monitoring (often a combination of patient blood glucose (BG) testing and/or continuous glucose monitoring (CGM)). |
| Closed loop without pramlintide | Experimental | Device: Closed loop without pramlintideThis visit is necessary to assess how well the closed loop system works without the pramlintide (how well it protects from hypoglycemia and hyperglycemia). It will be the exact protocol as for the closed loop with pramlintide but without the medication. |
| Open loop with pramlintide | Experimental | Drug: Open loop with pramlintideThe term open loop refers to insulin infusions regulated in their delivery based on patient self-monitoring and adjustment. The study subject will be in charge of their insulin treatment while also receiving pramlintide. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least six months (the diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determination are not needed).
- Age 21 to 65 years
- For females, not currently known to be pregnant
- An understanding of the protocol and a willingness to follow it
- HbA1c between 7 and 9%
Key exclusion criteria (35 listed)
- Known hypersensitivity to SYMLIN or any of its components, including metacresol
- Poor compliance with current insulin regimen
- Poor compliance with prescribed self-blood glucose monitoring
- HbA1c <7 or >9%
- Severe hypoglycemia resulting in seizure or loss of consciousness in the 2 weeks prior to enrollment
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 |
|---|---|---|
| Closed loop with pramlintideDose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily. | Drug | Closed loop with pramlintide |
| Closed loop without pramlintideThis visit will assess how well the closed loop system works without the pramlintide. | Device | Closed loop without pramlintide |
| Open loop with pramlintideDose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily. | Drug | Open loop with pramlintide |
Primary outcome
Percent of Blood glucose tests within target range of 70 to 180 mg/dl
Time frame: 24 hours
Percent of Blood glucose tests within target range of 70 to 180 mg/dl The primary outcome variable of glucose control within an American Diabetes Association (ADA) standard target range between 70 mg/dl to 180 mg/dl on a Yellow Springs Instrument (YSI) glucose analyzer. This is based upon the sample size estimate difference expected for % time within target range between artificial pancreas vs. patient control vs. Pramlintide plus artificial pancreas.
1 secondary outcome
Percent of Continuous Glucose Monitoring (CGM) System estimated blood glucose within target range of 70 to 180 mg/dl
Time frame: 72 hours
Results and safety
The study was stopped early (reason given: Modified study; created new study as a result of these modifications). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2014.
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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.
Anthony McCall, M.D., Ph.D. 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 Closed loop with pramlintide, Closed loop without pramlintide and Open loop with pramlintide 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 7 inclusion and 35 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 1 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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: Modified study; created new study as a result of these modifications). 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?
Percent of Blood glucose tests within target range of 70 to 180 mg/dl (time frame: 24 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 1 May 2014.