Diabetes Mellitus, Type IPhase 2NCT01781975
Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus
A Phase 2 study testing Imatinib Mesylate in people with Diabetes Mellitus, Type I and Diabetes Mellitus, Insulin-Dependent, 1, run by University of California, San Francisco at 9 sites in 2 countries.
Trial summary
Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing ß cells. Although exogenous insulin is widely available, it is not possible for affected individuals to consistently achieve euglycemia with current technology, and thus they are at risk for devastating long-term… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type I, Diabetes Mellitus, Insulin-Dependent, 1, Type 1 Diabetes Mellitus
- What is being tested?
- Imatinib Mesylate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Jan 2014to May 2018
- Phase
- Phase 2
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males and females age 12-45 years of age who meet the ADA standard T1DM criteria1. Positive for at least one islet cell autoantibody. Initial enrollment will be for subjects ages 18-45, with the goal to lower the age down to 12 upon acceptable safety review and prospect of benefit for this initial older cohort.
- Diagnosis of T1DM within 100 days of Visit 0.
- Peak stimulated C-peptide level >0.2 pmol/mL following an MMTT.
- Participants of childbearing age who are sexually active must agree to use an effective form of birth control (e.g., barrier method, oral contraception, or surgery). For females, these contraceptive measures must be maintained throughout the study; for males these measures must be followed for a minimum of 3 months after discontinuation of imatinib therapy.
Who cannot join
- Prior history of any significant cardiac disease such as congestive heart failure, myocardial infarction, arrhythmia, or structural defects or suspicion thereof.
- Leukopenia (<3,000 leukocytes/μL), neutropenia (<1,500 neutrophils/μL), or thrombocytopenia (<125,000 platelets/μL).
- Low Hemoglobin (baseline hemoglobin below lower limit of normal)
- Prior history of anaphylaxis, angioedema or serious cutaneous drug reactions
- Any sign of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, CMV, or toxoplasmosis), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, PPD, or HBSAg). Significant acute infections must be resolved before treatment may commence, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections.
- Anticipated ongoing use of diabetes medications other than insulin that affect glucose homeostasis, such as metformin, sulfonylureas, thiazolidinediones, glucagon-like peptide 1 (GLP-1) mimetics, dipeptidyl peptidase IV (DPP-IV) inhibitors, or amylin.
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- Prior or current treatment that is known to cause a significant, ongoing change in the course of T1DM or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids.
- Evidence of liver dysfunction, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 times the upper limit of normal persistent for 1 week or greater.
- Evidence of renal insufficiency as indicated by serum creatinine > 1.2 times the upper limit of normal and confirmed in a repeat test at least one week apart. Evidence of clinically significant metabolic bone disease (except adequately treated rickets).
- Females who are pregnant at the time of screening or unwilling to defer pregnancy during the 24-month study period.
- Prior treatment with imatinib or related tyrosine kinase inhibitor.
- Unable to avoid medications that affect CYP3A4: either inducers that may decrease imatinib levels, or inhibitors that may increase drug concentrations. (Refer to section 1.5.1.12 for a complete list of inducers and inhibitors.)
- Height standard deviation score ≥2 standard deviations below mean
- Any sign of QT prolongation on Visit -1 noted on ECG (> 450 ms in males and > 470 ms in females)
- Known coagulation disorders or use of anticoagulants
- Current and anticipated on-going treatment with drugs that may increase or decrease imatinib plasma concentrations (CYP3A4 family inhibitors or inducers) or drugs that may have their plasma concentration altered by imatinib (drugs metabolized by CYP3A4/5 and CYP2D6).
- Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Emory University
Atlanta, Georgia, 30322
Barbara Davis Center
Aurora, Colorado, 80045
Joslin Diabetes Center
Boston, Massachusetts, 02215
University of Texas Southwestern
Dallas, Texas, 75390
Indiana University
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of California-San Francisco
San Francisco, California, 94143
Australia1 site
Walter and Eliza Hall Institute of Medical Research
Melbourne, Victoria, 3050
About this study
Official title: Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-Onset Type 1 Diabetes Mellitus
Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing ß cells. Although exogenous insulin is widely available, it is not possible for affected individuals to consistently achieve euglycemia with current technology, and thus they are at risk for devastating long-term complications. This phase II study is designed to evaluate the safety and efficacy of imatinib mesylate as a novel therapy for new-onset T1DM. Imatinib is a first-in-class tyrosine kinase inhibitor.
This study will explore the potential role of short-term therapy with imatinib to induce tolerance and possibly lead to a durable long-term remission of T1DM.
Read the detailed description
Eligible participants will be randomized to receive either imatinib mesylate or placebo daily.
All participants randomized into this study will be seen at a study site for a follow-up evaluation, 2 weeks and 4 weeks after randomization, and every month month thereafter for the first year. Participants will come in for a visit ever 6 months for the second year.
At the study visits, participants will undergo assessments of their insulin production, immunologic status, and overall health. Subjects will be followed until the conclusion of the study. The trial is expected to last approximately 2-4 years or until the required amount of information is gathered.
- Conditions
- Diabetes Mellitus, Type I, Diabetes Mellitus, Insulin-Dependent, 1, Type 1 Diabetes Mellitus, Insulin-Dependent Diabetes Mellitus 1, IDDM
- Being tested
- Imatinib Mesylate, Placebo (For imatinib mesylate)
- 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.
Imatinib MesylateDrug
Also called GLEEVEC, Glivec
Placebo (For imatinib mesylate)Drug
| Study group | Role | What they receive |
|---|---|---|
| Imatinib Mesylate | Experimental | 400 mg imatinib given once daily basis. Receives: Drug: Imatinib Mesylate |
| Placebo | Placebo comparator | Placebo given once daily basis. Receives: Drug: Placebo (For imatinib mesylate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Stimulated C-peptide Curve (AUC) Mean Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 1 Year Visit
The primary outcome of each participant is the area under the stimulated c-peptide curve (AUC) mean based on data collected at time 0 to 2 hours of a 4-hour mixed meal tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30, 60, 90, and 120 minutes. The term "AUC mean" comes from the mean value theorem in calculus. It is the value on the scale of the y-axis that is equal to the AUC divided by the range on the x-axis (in this case 120 minutes).
Measured: Visit 9 (Week 52) at 0, 15, 30, 60, 90, 120 minutes post-dose
Secondary outcomes (5)
Area Under the Stimulated C-peptide Curve (AUC) Mean Over 4 Hours at 24 Months
Area under the MMTT-stimulated peak, 4 hour C-peptide AUC mean at week 104. The units are reported as nano-moles/Liter because this is AUC mean (the AUC is divided by the time internal so that the units return to the c-peptide units of measure).
Measured: Visit 13 (Week 104)
Change in HbA1c Levels Over Time
Change in HbA1c levels from Week 52 to Week 104
Measured: Visit 9 (Week 52) and Visit 13 (Week 104)
Change in Insulin Dose (Units/kg) Over Time
Assess insulin use in units per kilogram body weight per day at weeks 52 and 104.
Measured: Visit 9 (Week 52) and Visit 13 (Week 104)
Number of Severe Hypoglycemic Events
Major hypoglycemic events occurring from randomization at weeks 0, 52 and 104.
Measured: Visit 0 (Week 0), Visit 9 (Week 52), and Visit 13 (Week 104)
Number of Adverse Events
Number of adverse events that were reported throughout the study.
Measured: Adverse Events will be assessed at Visit 0 (week 0), Visit 1 (Week 2), Visit 2 (Week 4), and every month thereafter.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2013 (estimated)
- Study startJan 2014
- Primary completionMay 2017
- Study completionMay 2018
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 (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type IStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Responsible party
- Principal investigator, Stephen E. Gitelman, University of California, San Francisco
- Investigators
- Stephen E Gitelman, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01781975
- Sponsor's protocol ID
- 17-2013-6
- Status last verified
- Feb 2020
- First submitted
- 17 Jan 2013
- Last updated
- 11 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gitelman SE, Bundy BN, Ferrannini E, Lim N, Blanchfield JL, DiMeglio LA, Felner EI, Gaglia JL, Gottlieb PA, Long SA, Mari A, Mirmira RG, Raskin P, Sanda S, Tsalikian E, Wentworth JM, Willi SM, Krischer JP, Bluestone JA; Gleevec Trial Study Group. Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2021 Aug;9(8):502-514. doi: 10.1016/S2213-8587(21)00139-X. Epub 2021 Jun 29.
PubMed 34214479Robertson MA, Padgett LR, Fine JA, Chopra G, Mastracci TL. Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish. Islets. 2020 Sep 2;12(5):99-107. doi: 10.1080/19382014.2020.1791530. Epub 2020 Jul 25.
PubMed 32715853
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-Onset Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01781975
- Acronym / sponsor ID
- 17-2013-6
- Conditions
- Diabetes Mellitus, Type I, Diabetes Mellitus, Insulin-Dependent, 1, Type 1 Diabetes Mellitus, Insulin-Dependent Diabetes Mellitus 1, IDDM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Study start
- Jan 2014 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 1 Feb 2013 (estimated)
- Results
- Posted 8 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing ß cells. Although exogenous insulin is widely available, it is not possible for affected individuals to consistently achieve euglycemia with current technology, and thus they are at risk for devastating long-term complications. This phase II study is designed to evaluate the safety and efficacy of imatinib mesylate as a novel therapy for new-onset T1DM. Imatinib is a first-in-class tyrosine kinase inhibitor.
This study will explore the potential role of short-term therapy with imatinib to induce tolerance and possibly lead to a durable long-term remission of T1DM.
Detailed description
Eligible participants will be randomized to receive either imatinib mesylate or placebo daily.
All participants randomized into this study will be seen at a study site for a follow-up evaluation, 2 weeks and 4 weeks after randomization, and every month month thereafter for the first year. Participants will come in for a visit ever 6 months for the second year.
At the study visits, participants will undergo assessments of their insulin production, immunologic status, and overall health. Subjects will be followed until the conclusion of the study. The trial is expected to last approximately 2-4 years or until the required amount of information is gathered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib Mesylate | Experimental | Drug: Imatinib Mesylate400 mg imatinib given once daily basis. |
| Placebo | Placebo comparator | Drug: Placebo (For imatinib mesylate)Placebo given once daily basis. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Males and females age 12-45 years of age who meet the ADA standard T1DM criteria1. Positive for at least one islet cell autoantibody. Initial enrollment will be for subjects ages 18-45, with the goal to lower the age down to 12 upon acceptable safety review and prospect of benefit for this initial older cohort.
- Diagnosis of T1DM within 100 days of Visit 0.
- Peak stimulated C-peptide level >0.2 pmol/mL following an MMTT.
- Participants of childbearing age who are sexually active must agree to use an effective form of birth control (e.g., barrier method, oral contraception, or surgery). For females, these contraceptive measures must be maintained throughout the study; for males these measures must be followed for a minimum of 3 months after discontinuation of imatinib therapy.
Key exclusion criteria (17 listed)
- Prior history of any significant cardiac disease such as congestive heart failure, myocardial infarction, arrhythmia, or structural defects or suspicion thereof.
- Leukopenia (<3,000 leukocytes/μL), neutropenia (<1,500 neutrophils/μL), or thrombocytopenia (<125,000 platelets/μL).
- Low Hemoglobin (baseline hemoglobin below lower limit of normal)
- Prior history of anaphylaxis, angioedema or serious cutaneous drug reactions
- Any sign of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, CMV, or toxoplasmosis), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, PPD, or HBSAg). Significant acute infections must be resolved before treatment may commence, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections.
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 |
|---|---|---|
| Imatinib MesylateAlso: GLEEVEC, Glivec | Drug | Imatinib Mesylate |
| Placebo (For imatinib mesylate) | Drug | Placebo |
Primary outcome
Area Under the Stimulated C-peptide Curve (AUC) Mean Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 1 Year Visit
Time frame: Visit 9 (Week 52) at 0, 15, 30, 60, 90, 120 minutes post-dose
The primary outcome of each participant is the area under the stimulated c-peptide curve (AUC) mean based on data collected at time 0 to 2 hours of a 4-hour mixed meal tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30, 60, 90, and 120 minutes. The term "AUC mean" comes from the mean value theorem in calculus. It is the value on the scale of the y-axis that is equal to the AUC divided by the range on the x-axis (in this case 120 minutes).
5 secondary outcomes
Area Under the Stimulated C-peptide Curve (AUC) Mean Over 4 Hours at 24 Months
Time frame: Visit 13 (Week 104)
Change in HbA1c Levels Over Time
Time frame: Visit 9 (Week 52) and Visit 13 (Week 104)
Change in Insulin Dose (Units/kg) Over Time
Time frame: Visit 9 (Week 52) and Visit 13 (Week 104)
Number of Severe Hypoglycemic Events
Time frame: Visit 0 (Week 0), Visit 9 (Week 52), and Visit 13 (Week 104)
Number of Adverse Events
Time frame: Adverse Events will be assessed at Visit 0 (week 0), Visit 1 (Week 2), Visit 2 (Week 4), and every month thereafter.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34214479Gitelman SE, Bundy BN, Ferrannini E, Lim N, Blanchfield JL, DiMeglio LA, Felner EI, Gaglia JL, Gottlieb PA, Long SA, Mari A, Mirmira RG, Raskin P, Sanda S, Tsalikian E, Wentworth JM, Willi SM, Krischer JP, Bluestone JA; Gleevec Trial Study Group. Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2021 Aug;9(8):502-514. doi: 10.1016/S2213-8587(21)00139-X. Epub 2021 Jun 29.
- Derived from this study: PubMed 32715853Robertson MA, Padgett LR, Fine JA, Chopra G, Mastracci TL. Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish. Islets. 2020 Sep 2;12(5):99-107. doi: 10.1080/19382014.2020.1791530. Epub 2020 Jul 25.
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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.
Stephen E Gitelman, MD principal investigator
University of California, San Francisco
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib Mesylate in people with Diabetes Mellitus, Type I and Diabetes Mellitus, Insulin-Dependent, 1, run by University of California, San Francisco at 9 sites in 2 countries.
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 4 inclusion and 17 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 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Australia. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 8 Aug 2018). 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?
Area Under the Stimulated C-peptide Curve (AUC) Mean Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 1 Year Visit (time frame: Visit 9 (Week 52) at 0, 15, 30, 60, 90, 120 minutes post-dose). 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 NCT01781975, which also lists 2 linked publications.
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 11 Feb 2020.