Type 1 Diabetes MellitusPhase 2NCT06474598
An Adaptive Design Study of MTX228
A Phase 2 study testing MTX228 and DEXCOM G6 in people with Type 1 Diabetes Mellitus, run by University of Alberta at 1 site in Canada.
Trial summary
MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes. Promoting the re-growth of lost beta cells would be beneficial to people with Type 1 Diabetes because it would allow them to take less insulin by injection and would improve their… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- MTX228 and DEXCOM G6
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- 14 Nov 2024to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- clinical diagnosis of T1DM with onset before the age of 35 requiring continuous treatment with insulin within 1 year of diagnosis and the presence of positive T1DM autoantibody titer if diagnosed after age 35 (past or present
- HbA1c between 6.0 - 10.0 %.
- Willing to wear study-provided CGM and share CGM data via cloud.
- Diagnosis of T1DM ≥1year at time of screening.
- Fasting or random (post-prandial) C-peptide level ≥ 100 pmol/l (or 0.3 ng/mL) during screening or pre-screening. Pre-screening C-peptide levels may be obtained by the study team (subject to patient's written consent) up to 56 days before planned enrolment to reduce the number of screen failures.
- BMI ≤ 35 kg/m2
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- eGFR >45 ml/min/1.73m2
- Able and willing to comply with the study protocol for the duration of the study
- Written informed consent must be obtained before any study-related assessment is performed.
Who cannot join
- Diagnosis or history indicative of monogenic, Type 2 or post-pancreatectomy diabetes
- History of >1 episode of severe (level 3) hypoglycemia in the prior 6 months
- Significant cardiovascular history defined as:
- History of myocardial infarction, coronary angioplasty or bypass grafts, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accidents within six months prior to entry into the study
- Congestive heart failure defined as New York Heart Association (NYHA) stage III and IV
- Uncontrolled hypertension defined as SBP > 160 mmHg and/or DBP > 100 mmHg
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- Symptomatic postural hypotension
- Use of systemic corticosteroids (except physiologic replacement doses for adrenal insufficiency) or other medications that would influence insulin sensitivity
- Use of non-insulin antihyperglycemic agents within prior 30 days.
- History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder including previous solid organ or cell transplant that would impact patient safety or data interpretation.
- History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years before screening (any history of treated cervical intraepithelial neoplasia is allowed)
- Known recreational substance use or psychiatric illness that, in the opinion of the Investigator, may impact the safety of the subject or objectives with scheduled visits
- A history of alcohol or drug abuse or drug addiction in the previous 12 months
- A positive pregnancy blood test for women of childbearing age or breast-feeding women 12 Are unwilling to use an "effective" method of contraception during the course of the study. Sexually active male patients, who could have children, are required to use a condom or abstained from intercourse, and refrain from sperm donation for the purposes of conception. Females have to be surgically sterile (via hysterectomy or bilateral tubal ligation) or post-menopausal or using a medically acceptable barrier method of contraception (i.e. IUD, barrier methods with spermicide or abstinence).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Peter Senior contact
Canada1 site, 1 recruiting
- Recruiting
University of Alberta
Edmonton, Alberta, T6G 2R3
Dominque Forrest, dforres1@ualberta.ca
Peter Senior, MD, psenior@ualberta.ca
About this study
Official title: A Open Label, Parallel Group Phase IIA, Adaptive Design Study of MTX228 in Adult Subjects With Type 1 Diabetes and Preserved β-Cell Function
MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes. Promoting the re-growth of lost beta cells would be beneficial to people with Type 1 Diabetes because it would allow them to take less insulin by injection and would improve their overall blood sugar control while reducing the risk and rate of low blood sugars. This open-label dose selection study aims to determine the optimal dose ofMTX228 for use in a future phase IIb study.
The purpose is to investigate the relative effectiveness of different doses of MTX228 and to select the most effective dose for further investigation in a phase 2b study.
Read the detailed description
MTX228 was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, MTX228 has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as MTX228, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabetes.
MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 diabetes, where lower doses (100 mg once or twice daily) were more effective than higher doses (200 mg once or twice daily). The purpose of this study is to compare the effect of different doses of MTX228 in order to determine the most effective dose to move forward in a subsequent phase 2b study.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- MTX228, DEXCOM G6
- 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.
MTX228Drug
Also called Tolimidone
Tolimidone was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, tolimidone has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as Tolimidone, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabete
DEXCOM G6Device
To monitor participants blood glucose levels continuously
| Study group | Role | What they receive |
|---|---|---|
| 100 mg QD | Active comparator | Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg QD dose Receives: Drug: MTX228; Device: DEXCOM G6 |
| 100 mg BID | Active comparator | Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg BID dose Receives: Drug: MTX228; Device: DEXCOM G6 |
| 200 mg QD | Active comparator | Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 200mg BID dose Receives: Drug: MTX228; Device: DEXCOM G6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in AUC C-peptide
C-peptide level as it relates to MTX228 doses
Change in postprandial C-peptide level area under the curve (AUC), in a 2-hour Mixed Meal Tolerance Test (MMTT), between Days 0 and 84, as well as a change in AUC C-peptide between subjects receiving different doses of MTX228.
Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.
Measured: Days 0 and 84
Dose selection for phase IIb study
A change in AUC C-peptide between subjects receiving different doses of MTX228 will determine the best doses
Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.
Measured: Days 0 and 84
Secondary outcomes (6)
Lowered or increased total daily insulin dose
Changes in total daily insulin dose will be monitored as per:
•Change in daily insulin use as recorded in subject's journal
To observe if an increase in MTX228 will decrease daily insulin usage
Measured: Days 84 and 168
To assess the time spent in a plasma glucose range of 3.9-10.0 mol/L
Changes in total daily insulin dose will be monitored based upon continuous glucose monitoring (CGM) Which dose of MTX228 helps facilitate a longer period of time spent in this optimal plasma glucose range
Measured: Days 84 and 168
Time spent in high range (10.1-13.9 mmol/L) and very high range (>13.9) based upon CGM in the last two weeks of the main treatment period and separately of the extended treatment
Changes in total daily insulin dose will be monitored based on continuous glucose monitoring (CGM)
Assessing which dose of MTX228 is least effective at keeping the participant out of the high and very high range. This will help aide in the dose selection phase
Measured: Days 84 and 168
Change in HbA1c
Changes in total daily insulin dose will be monitored as per CGM and blood tests.
Ideally, HbA1c should be lowered over time with an increased dose of MTX228
Measured: Days 84 and 168
Change in fasting plasma glucose (FPG)
If the beneficial metabolic effects are mediated by an expansion of beta cell mass they should persist during the washout period.
Measured: Days 84 and 168
The number of episodes of level 2 and 3 hypoglycemia in study participants
The number and duration of level 2 and 3 hypoglycemic events based upon CGM throughout treatment and follow up. Ideal doses of MTX228 should decrease the number of episodes for participants.
Measured: Days 84 and 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2024
- Study start14 Nov 2024
- Primary completionOct 2026 (estimated)
- Study completionDec 2027 (estimated)
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 AlbertaThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06474598
- Sponsor's protocol ID
- MTX228-2024
- Status last verified
- Apr 2026
- First submitted
- 8 Apr 2024
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Open Label, Parallel Group Phase IIA, Adaptive Design Study of MTX228 in Adult Subjects With Type 1 Diabetes and Preserved β-Cell Function
- ClinicalTrials.gov ID
- NCT06474598
- Acronym / sponsor ID
- MTX228-2024
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- 14 Nov 2024 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 25 Jun 2024 (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.
MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes. Promoting the re-growth of lost beta cells would be beneficial to people with Type 1 Diabetes because it would allow them to take less insulin by injection and would improve their overall blood sugar control while reducing the risk and rate of low blood sugars. This open-label dose selection study aims to determine the optimal dose ofMTX228 for use in a future phase IIb study.
The purpose is to investigate the relative effectiveness of different doses of MTX228 and to select the most effective dose for further investigation in a phase 2b study.
Detailed description
MTX228 was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, MTX228 has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as MTX228, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabetes.
MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 diabetes, where lower doses (100 mg once or twice daily) were more effective than higher doses (200 mg once or twice daily). The purpose of this study is to compare the effect of different doses of MTX228 in order to determine the most effective dose to move forward in a subsequent phase 2b study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 100 mg QD | Active comparator | Drug: MTX228, Device: DEXCOM G6Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg QD dose |
| 100 mg BID | Active comparator | Drug: MTX228, Device: DEXCOM G6Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg BID dose |
| 200 mg QD | Active comparator | Drug: MTX228, Device: DEXCOM G6Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 200mg BID dose |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- clinical diagnosis of T1DM with onset before the age of 35 requiring continuous treatment with insulin within 1 year of diagnosis and the presence of positive T1DM autoantibody titer if diagnosed after age 35 (past or present
- HbA1c between 6.0 - 10.0 %.
- Willing to wear study-provided CGM and share CGM data via cloud.
- Diagnosis of T1DM ≥1year at time of screening.
- Fasting or random (post-prandial) C-peptide level ≥ 100 pmol/l (or 0.3 ng/mL) during screening or pre-screening. Pre-screening C-peptide levels may be obtained by the study team (subject to patient's written consent) up to 56 days before planned enrolment to reduce the number of screen failures.
Key exclusion criteria (14 listed)
- Diagnosis or history indicative of monogenic, Type 2 or post-pancreatectomy diabetes
- History of >1 episode of severe (level 3) hypoglycemia in the prior 6 months
- Significant cardiovascular history defined as:
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 |
|---|---|---|
| MTX228Also: TolimidoneTolimidone was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, tolimidone has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as Tolimidone, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabete | Drug | 100 mg BID, 100 mg QD, 200 mg QD |
| DEXCOM G6To monitor participants blood glucose levels continuously | Device | 100 mg BID, 100 mg QD, 200 mg QD |
Primary outcome
Change in AUC C-peptide
Time frame: Days 0 and 84
C-peptide level as it relates to MTX228 doses Change in postprandial C-peptide level area under the curve (AUC), in a 2-hour Mixed Meal Tolerance Test (MMTT), between Days 0 and 84, as well as a change in AUC C-peptide between subjects receiving different doses of MTX228. Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.
Dose selection for phase IIb study
Time frame: Days 0 and 84
A change in AUC C-peptide between subjects receiving different doses of MTX228 will determine the best doses Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.
6 secondary outcomes
Lowered or increased total daily insulin dose
Time frame: Days 84 and 168
To assess the time spent in a plasma glucose range of 3.9-10.0 mol/L
Time frame: Days 84 and 168
Time spent in high range (10.1-13.9 mmol/L) and very high range (>13.9) based upon CGM in the last two weeks of the main treatment period and separately of the extended treatment
Time frame: Days 84 and 168
Change in HbA1c
Time frame: Days 84 and 168
Change in fasting plasma glucose (FPG)
Time frame: Days 84 and 168
The number of episodes of level 2 and 3 hypoglycemia in study participants
Time frame: Days 84 and 168
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
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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.
Peter Senior contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MTX228 and DEXCOM G6 in people with Type 1 Diabetes Mellitus, run by University of Alberta at 1 site in Canada.
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 9 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 13 Apr 2026. 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 Canada. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dominique Forrest (7802481770, dforres1@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in AUC C-peptide (time frame: Days 0 and 84). 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 13 Apr 2026.