Type 1 Diabetes MellitusPhase 2/3NCT03262116
Individualizing Automated Closed Loop Glucose Control Through Pharmacokinetic Profiling in an Insulin-Only Bionic Pancreas
A Phase 2/3 study testing Humalog, Novolog and BC222 insulin lispro in people with Type 1 Diabetes Mellitus, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Subjects will participate in three weeks of the bionic pancreas in the insulin-only configuration. Each week, subjects will use a different rapid acting insulin analog -- Humalog, Novolog, or BC222 insulin lispro -- in a randomized cross-over order. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Humalog, Novolog and BC222 insulin lispro
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2019to 23 Jul 2019
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years and have had clinical type 1 diabetes for at least one year
- Diabetes managed using an insulin pump for ≥ 6 months
- Have used a CGM for at least one cumulative month over the last 12 months
- Prescription medication regimen stable for > 1 month (except for medications that will not affect the safety of the study and are not expected to affect any outcome of the study, in the judgment of the principal investigator)
- Willing to remain within a 250 mile radius of MGH. No air travel will be allowed, and subjects will still be expected to follow the visit schedule as described.
- Willing to wear one Dexcom CGM sensor, and one leur-lock compatible infusion set that must be replaced every other day
- Have a mobile phone they will have access to at all times during the study for making contact with study staff
Who cannot join
- Unable to provide informed consent (e.g. impaired cognition or judgment)
- Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the bionic pancreas, impaired memory, unable to speak and read English)
- Current participation in another diabetes-related clinical trial that, in the judgment of the principal investigator, will compromise the results of this study or the safety of the subject
- Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception Subjects must use acceptable contraception for the two weeks prior to the study, throughout the study and for the two weeks following the study.
- Acceptable contraception methods include: Oral contraceptive pill (OCP), Intrauterine Device (IUD, hormonal or copper), Male condoms, Female condoms, Diaphragm or cervical cap with spermicide, Contraceptive patch (such as OrthoEvra), Contraceptive implant (such as Implanon, Nexplanon), Vaginal ring (such as NuvaRing), Progestin shot (such as Depo-Provera), Male partner with a vasectomy proven to be effective by semen analysis
- Current alcohol abuse (intake averaging > 3 drinks daily in last 30 days) or other substance abuse (use within the last 6 months of controlled substances other than marijuana without a prescription)
Show all 26Show fewer
- Unwilling or unable or to avoid use of drugs that may dull the sensorium, reduce sensitivity to symptoms of hypoglycemia, or hinder decision making during the period of participation in the study (use of beta blockers will be allowed as long as the dose is stable and the subject does not meet the criteria for hypoglycemia unawareness while taking that stable dose, but use of benzodiazepines or narcotics or other central nervous system depressants, even if by prescription, may be excluded according to the judgment of the principal investigator)
- Renal failure requiring dialysis
- Estimated Glomerular filtration rate <15 mL/min/1.732
- Personal history of cystic fibrosis, severe pancreatitis, pancreatic tumor, pancreatectomy or any other pancreatic disease leading to diabetes mellitus.
- Any known history of coronary artery disease including, but not limited to, history of myocardial infarction, stress test showing ischemia, history of angina, or history of intervention such as coronary artery bypass grafting, percutaneous coronary intervention, or enzymatic lysis of a presumed coronary occlusion)
- Abnormal EKG consistent with coronary artery disease or increased risk of malignant arrhythmia including, but not limited to, evidence of active ischemia, prior myocardial infarction, proximal LAD critical stenosis (Wellen's sign), prolonged QT interval (> 440 ms). Non-specific ST segment and T wave changes are not grounds for exclusion in the absence of symptoms or history of heart disease. A reassuring evaluation by a cardiologist after an abnormal EKG finding may allow participation.
- Congestive heart failure (established history of CHF, lower extremity edema, paroxysmal nocturnal dyspnea, or orthopnea)
- History of TIA or stroke15. Recent history of diabetic ketoacidosis (DKA) or severe hypoglycemia in the last 6 months. Severe hypoglycemia is defined as an event that required assistance of another person due to altered consciousness, and required another person to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure or coma.
- History of more than 1 episode of DKA requiring hospitalization in the last 2 years
- History of more than 1 episode of severe hypoglycemia in the last year.
- Untreated or inadequately treated mental illness (indicators would include symptoms such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the last year), or treatment with anti-psychotic medications that are known to affect glucose regulation.
- Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference
- Unable to completely avoid acetaminophen for duration of study
- Established history of allergy or severe reaction to adhesive or tape that must be used in the study
- History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight
- History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
- Use of oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, DPP-4 inhibitors, SGLT-2 inhibitors) or non-insulin injectable (GLP-1 agonists, amylin) anti-diabetic medications
- Any diagnosed allergy to insulin lispro or insulin aspart
- Lives in or frequents areas with poor Verizon wireless network coverage (which would prevent study staff from contacting subjects)
- Any factors that, in the opinion of the principal investigator would interfere with the safe completion of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Subjects will participate in three weeks of the bionic pancreas in the insulin-only configuration. Each week, subjects will use a different rapid acting insulin analog -- Humalog, Novolog, or BC222 insulin lispro -- in a randomized cross-over order.
Read the detailed description
The investigators hypothesize that differences in the PK characteristics of insulin analogs will lead to differences in glycemic outcomes when delivered by the insulin-only configuration of the bionic pancreas. Specifically, the investigators predict that insulin analogs that have faster absorption (numerically lower Tmax and/or T½max) and insulin analogs that have faster clearance (numerically lower terminal half-life) will result in lower mean glucose and/or a lower percentage of time in the hypoglycemic range.
Up to 30 subjects will participate in three 7-day study arms using insulin lispro, insulin aspart, and BC222 lispro in the bionic pancreas in random order. The co-primary outcomes will be mean CGMG and fraction of time spent with CGMG <54 mg/dl with comparisons made between arms for individual participants. Secondary analyses will include time in glycemic ranges (<50, <60, <70, 70-120, 70-180, >180, >250 mg/dl), coefficient of variation, mean postprandial excursion (difference in CGMG from the time of meal announcement to the peak CGMG in the first 4 hours after the meal announcement) for both mixed meal challenges, number of symptomatic hypoglycemic events, grams of carbohydrate consumed to treat hypoglycemia, and TDD of insulin, between arms for individual subjects.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Humalog, Novolog, BC222 insulin lispro, Bionic Pancreas
- Keywords
- bionic pancreas, insulin, continuous glucose monitor, type 1 diabetes, insulin pharmacokinetics
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HumalogDrug
Also called insulin
Subjects will participate in one week of wearing the insulin only bionic pancreas using humalog as the rapid acting insulin.
NovologDrug
Also called insulin
Subjects will participate in one week of wearing the insulin only bionic pancreas using novolog as the rapid acting insulin.
BC222 insulin lisproDrug
Also called insulin
Subjects will participate in one week of wearing the insulin only bionic pancreas using BC222 insulin lispro as the rapid acting insulin.
Bionic PancreasDevice
The insulin-only bionic pancreas will be used in all three arms of the study
| Study group | Role | What they receive |
|---|---|---|
| Bionic Pancreas - Humalog | Experimental | Subjects will participate in one week of wearing the insulin only bionic pancreas using humalog as the rapid acting insulin. Receives: Drug: Humalog; Device: Bionic Pancreas |
| Bionic Pancreas - Novolog | Experimental | Subjects will participate in one week of wearing the insulin only bionic pancreas using novolog as the rapid acting insulin. Receives: Drug: Novolog; Device: Bionic Pancreas |
| Bionic Pancreas - BC222 insulin lispro | Experimental | Subjects will participate in one week of wearing the insulin only bionic pancreas using BC222 insulin lispro as the rapid acting insulin. Receives: Drug: BC222 insulin lispro; Device: Bionic Pancreas |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Continuous Glucose Monitor (CGM) Glucose
The average glucose achieved by the bionic pancreas as measured by the continuous glucose monitor during each arm
Measured: 7 days
Percentage of Time Spent With CGM Glucose < 54 mg/dl
The amount of time the subject spent in the hypoglycemic range < 54 mg/dl as measured by the continuous glucose monitor during each arm
Measured: 7 days
Secondary outcomes (6)
Percentage of Time Spent Within Each of the Following Ranges:
The amount of time subject's spent in each of the listed glucose ranges as measured by the continuous glucose monitor during each bionic pancreas arm
Measured: 7 days
Within Day Coefficient of Variation
A measure of dispersion of glucose values around the mean
Measured: 7 days
Mean Post Prandial Excursion
Difference in CGMG from the beginning of the meal challenge to the peak CGMG in the 4 hours after the meal, for both mixed meal challenges.
Measured: 7 days
Number of Symptomatic Hypoglycemic Events Per Day
The number of times subjects report experiencing symptoms of hypoglycemia during each bionic pancreas arm
Measured: 7 days
Grams of Carbohydrates Consumed to Treat Hypoglycemia Per Day
The total amount of grams of carbohydrates subjects report having to take in for treatment of hypoglycemia
Measured: 7 days
Total Daily Dose of Insulin
The average total amount of insulin delivered daily by the bionic pancreas during each bionic pancreas arm.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start19 Mar 2019
- Primary completion23 Jul 2019
- Study completion23 Jul 2019
Why it stopped: Devices are not available
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.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University
- Responsible party
- Principal investigator, Steven J. Russell, MD, PhD, Massachusetts General Hospital
- Investigators
- Steven J Russell, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03262116
- Sponsor's protocol ID
- 2017P001778
- Status last verified
- Nov 2022
- First submitted
- 23 Aug 2017
- Last updated
- 9 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualizing Automated Closed Loop Glucose Control Through Pharmacokinetic Profiling in an Insulin-Only Bionic Pancreas
- ClinicalTrials.gov ID
- NCT03262116
- Acronym / sponsor ID
- 2017P001778
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- bionic pancreas, insulin, continuous glucose monitor, type 1 diabetes, insulin pharmacokinetics
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Devices are not available
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Boston University
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- 23 Jul 2019 (actual)
- Study completion
- 23 Jul 2019 (actual)
- First posted
- 25 Aug 2017 (actual)
- Results
- Posted 9 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subjects will participate in three weeks of the bionic pancreas in the insulin-only configuration. Each week, subjects will use a different rapid acting insulin analog -- Humalog, Novolog, or BC222 insulin lispro -- in a randomized cross-over order.
Detailed description
The investigators hypothesize that differences in the PK characteristics of insulin analogs will lead to differences in glycemic outcomes when delivered by the insulin-only configuration of the bionic pancreas. Specifically, the investigators predict that insulin analogs that have faster absorption (numerically lower Tmax and/or T½max) and insulin analogs that have faster clearance (numerically lower terminal half-life) will result in lower mean glucose and/or a lower percentage of time in the hypoglycemic range.
Up to 30 subjects will participate in three 7-day study arms using insulin lispro, insulin aspart, and BC222 lispro in the bionic pancreas in random order. The co-primary outcomes will be mean CGMG and fraction of time spent with CGMG <54 mg/dl with comparisons made between arms for individual participants. Secondary analyses will include time in glycemic ranges (<50, <60, <70, 70-120, 70-180, >180, >250 mg/dl), coefficient of variation, mean postprandial excursion (difference in CGMG from the time of meal announcement to the peak CGMG in the first 4 hours after the meal announcement) for both mixed meal challenges, number of symptomatic hypoglycemic events, grams of carbohydrate consumed to treat hypoglycemia, and TDD of insulin, between arms for individual subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bionic Pancreas - Humalog | Experimental | Drug: Humalog, Device: Bionic PancreasSubjects will participate in one week of wearing the insulin only bionic pancreas using humalog as the rapid acting insulin. |
| Bionic Pancreas - Novolog | Experimental | Drug: Novolog, Device: Bionic PancreasSubjects will participate in one week of wearing the insulin only bionic pancreas using novolog as the rapid acting insulin. |
| Bionic Pancreas - BC222 insulin lispro | Experimental | Drug: BC222 insulin lispro, Device: Bionic PancreasSubjects will participate in one week of wearing the insulin only bionic pancreas using BC222 insulin lispro as the rapid acting insulin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years and have had clinical type 1 diabetes for at least one year
- Diabetes managed using an insulin pump for ≥ 6 months
- Have used a CGM for at least one cumulative month over the last 12 months
- Prescription medication regimen stable for > 1 month (except for medications that will not affect the safety of the study and are not expected to affect any outcome of the study, in the judgment of the principal investigator)
- Willing to remain within a 250 mile radius of MGH. No air travel will be allowed, and subjects will still be expected to follow the visit schedule as described.
Key exclusion criteria (26 listed)
- Unable to provide informed consent (e.g. impaired cognition or judgment)
- Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the bionic pancreas, impaired memory, unable to speak and read English)
- Current participation in another diabetes-related clinical trial that, in the judgment of the principal investigator, will compromise the results of this study or the safety of the subject
- Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception Subjects must use acceptable contraception for the two weeks prior to the study, throughout the study and for the two weeks following the study.
- Acceptable contraception methods include: Oral contraceptive pill (OCP), Intrauterine Device (IUD, hormonal or copper), Male condoms, Female condoms, Diaphragm or cervical cap with spermicide, Contraceptive patch (such as OrthoEvra), Contraceptive implant (such as Implanon, Nexplanon), Vaginal ring (such as NuvaRing), Progestin shot (such as Depo-Provera), Male partner with a vasectomy proven to be effective by semen analysis
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 |
|---|---|---|
| HumalogAlso: insulinSubjects will participate in one week of wearing the insulin only bionic pancreas using humalog as the rapid acting insulin. | Drug | Bionic Pancreas - Humalog |
| NovologAlso: insulinSubjects will participate in one week of wearing the insulin only bionic pancreas using novolog as the rapid acting insulin. | Drug | Bionic Pancreas - Novolog |
| BC222 insulin lisproAlso: insulinSubjects will participate in one week of wearing the insulin only bionic pancreas using BC222 insulin lispro as the rapid acting insulin. | Drug | Bionic Pancreas - BC222 insulin lispro |
| Bionic PancreasThe insulin-only bionic pancreas will be used in all three arms of the study | Device | Bionic Pancreas - BC222 insulin lispro, Bionic Pancreas - Humalog, Bionic Pancreas - Novolog |
Primary outcome
Average Continuous Glucose Monitor (CGM) Glucose
Time frame: 7 days
The average glucose achieved by the bionic pancreas as measured by the continuous glucose monitor during each arm
Percentage of Time Spent With CGM Glucose < 54 mg/dl
Time frame: 7 days
The amount of time the subject spent in the hypoglycemic range < 54 mg/dl as measured by the continuous glucose monitor during each arm
6 secondary outcomes
Percentage of Time Spent Within Each of the Following Ranges:
Time frame: 7 days
Within Day Coefficient of Variation
Time frame: 7 days
Mean Post Prandial Excursion
Time frame: 7 days
Number of Symptomatic Hypoglycemic Events Per Day
Time frame: 7 days
Grams of Carbohydrates Consumed to Treat Hypoglycemia Per Day
Time frame: 7 days
Total Daily Dose of Insulin
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Steven J Russell, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Humalog, Novolog and BC222 insulin lispro in people with Type 1 Diabetes Mellitus, run by Massachusetts General Hospital 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 26 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 9 Dec 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.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2022). 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?
Average Continuous Glucose Monitor (CGM) Glucose (time frame: 7 days). The study lists 2 primary outcomes in all. 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 9 Dec 2022.