Type 1 DiabetesPhase 2/3NCT04409795
Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study
A Phase 2/3 study testing Metformin Extended Release Oral Tablet and Sitagliptin in people with Type 1 Diabetes and Monogenic Diabetes, run by Joslin Diabetes Center at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent diabetes. Read more about this study
- Who is it for?
- Ages Up to 85 years
- Conditions the study is for
- Type 1 Diabetes, Monogenic Diabetes
- What is being tested?
- Metformin Extended Release Oral Tablet and Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2021to 31 Dec 2024
- Phase
- Phase 2/3
- 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 Up to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Existing participants in the Joslin 50-Year Medalist Study
- Residing in the United States
- Capable of giving informed consent
- Known detectable C-peptide >0.05 ng/mL
Who cannot join
- Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis, lupus, and inflammatory bowel disease
- Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure, angina, stroke, or uncontrolled hypertension>160/100 during the past 3 months
- Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease
- Pre-existing liver disease or liver function tests (AST or ALT)>3x the upper limit of normal
- Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated glomerular filtration rate<45 mL/min/1.73 m2)
- Active use of immunosuppressants
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- Recipients of prior islet cell or pancreas transplantation
- Inability to travel due to frailty or health reasons
- Donated blood within the previous two (2) months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Trial of Adding Oral Hypoglycemic Therapy to Insulin Treatment in Monogenic Variant Carriers of the Joslin 50-Year Medalist Study
The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent diabetes. Our primary objective is to evaluate whether the presence of human leukocyte antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of OHA in these subjects.
- Conditions
- Type 1 Diabetes, Monogenic Diabetes
- Being tested
- Metformin Extended Release Oral Tablet, Sitagliptin
- 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.
Metformin Extended Release Oral TabletDrug
Initial oral hypoglycemic agent added to existing insulin treatment
SitagliptinDrug
Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)
| Study group | Role | What they receive |
|---|---|---|
| HLA+ Group | Other | Participants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score>0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-) Receives: Drug: Metformin Extended Release Oral Tablet; Drug: Sitagliptin |
| HLA- Group | Other | Participants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score>0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff Receives: Drug: Metformin Extended Release Oral Tablet; Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycated hemoglobin (HbA1c)
Change in HbA1c (%) between the two study groups
Measured: 3 months and 6 months
Secondary outcomes (8)
Daily insulin dose
Change in daily insulin dose (units/kg body weight) between the two study groups
Measured: 3 months and 6 months
Body mass index (BMI)
Change in BMI between the two study groups. Weight and height will be combined to report BMI in kg/m^2.
Measured: 3 months and 6 months
C-peptide
Change in C-peptide (ng/mL) between the two study groups
Measured: 3 months and 6 months
Total cholesterol
Change in total cholesterol (mg/dL) between the two study groups
Measured: 3 months and 6 months
Low density lipoprotein (LDL)-cholesterol
Change in LDL-cholesterol (mg/dL) between the two study groups
Measured: 3 months and 6 months
High density lipoprotein (HDL)-cholesterol
Change in HDL-cholesterol (mg/dL) between the two study groups
Measured: 3 months and 6 months
Triglycerides
Change in triglycerides (mg/dL) between the two study groups
Measured: 3 months and 6 months
Area under the plasma concentration versus time curve (AUC) of C-peptide
Change in AUC of C-peptide between the two study groups, as measured by the hyperglycemic/arginine clamp, at the end of the study
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2020
- Study start26 Aug 2021
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joslin Diabetes Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- George L. King, MD, Principal investigator, Joslin Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04409795
- Sponsor's protocol ID
- 2019-76
- Status last verified
- Feb 2025
- First submitted
- 14 Nov 2019
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Adding Oral Hypoglycemic Therapy to Insulin Treatment in Monogenic Variant Carriers of the Joslin 50-Year Medalist Study
- ClinicalTrials.gov ID
- NCT04409795
- Acronym / sponsor ID
- 2019-76
- Conditions
- Type 1 Diabetes, Monogenic Diabetes
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Joslin Diabetes CenterUniversity, hospital or other
- Study start
- 26 Aug 2021 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 1 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent diabetes. Our primary objective is to evaluate whether the presence of human leukocyte antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of OHA in these subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HLA+ Group | Other | Drug: Metformin Extended Release Oral Tablet, Drug: SitagliptinParticipants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score>0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-) |
| HLA- Group | Other | Drug: Metformin Extended Release Oral Tablet, Drug: SitagliptinParticipants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score>0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff |
Who may qualify
- Ages
- Up to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Existing participants in the Joslin 50-Year Medalist Study
- Residing in the United States
- Capable of giving informed consent
- Known detectable C-peptide >0.05 ng/mL
Key exclusion criteria (9 listed)
- Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis, lupus, and inflammatory bowel disease
- Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure, angina, stroke, or uncontrolled hypertension>160/100 during the past 3 months
- Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease
- Pre-existing liver disease or liver function tests (AST or ALT)>3x the upper limit of normal
- Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated glomerular filtration rate<45 mL/min/1.73 m2)
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 |
|---|---|---|
| Metformin Extended Release Oral TabletInitial oral hypoglycemic agent added to existing insulin treatment | Drug | HLA+ Group, HLA- Group |
| SitagliptinSecondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin) | Drug | HLA+ Group, HLA- Group |
Primary outcome
Glycated hemoglobin (HbA1c)
Time frame: 3 months and 6 months
Change in HbA1c (%) between the two study groups
8 secondary outcomes
Daily insulin dose
Time frame: 3 months and 6 months
Body mass index (BMI)
Time frame: 3 months and 6 months
C-peptide
Time frame: 3 months and 6 months
Total cholesterol
Time frame: 3 months and 6 months
Low density lipoprotein (LDL)-cholesterol
Time frame: 3 months and 6 months
High density lipoprotein (HDL)-cholesterol
Time frame: 3 months and 6 months
Triglycerides
Time frame: 3 months and 6 months
Area under the plasma concentration versus time curve (AUC) of C-peptide
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
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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.
George L. King, MD principal investigator
Joslin Diabetes Center
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 Metformin Extended Release Oral Tablet and Sitagliptin in people with Type 1 Diabetes and Monogenic Diabetes, run by Joslin Diabetes Center 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 4 inclusion and 9 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 24 Feb 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Glycated hemoglobin (HbA1c) (time frame: 3 months and 6 months). 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 24 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.