Type 1 DiabetesPhase 2NCT02580877
Immune Effects of Oral Insulin in Relatives at Risk for Type 1 Diabetes Mellitus (TN20)
A Phase 2 study testing 67.5 mg oral insulin crystals daily and 500mg oral insulin crystals every other week in people with Type 1 Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 19 sites in 4 countries.
Trial summary
The study is a 2 arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D). Read more about this study
- Who is it for?
- Ages 3 to 45 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- 67.5 mg oral insulin crystals daily and 500mg oral insulin crystals every other week
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 19 sitesin 4 countries
- Study dates
- Jan 2016to Mar 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 3 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants in TrialNet Natural History/Pathway to Prevention Study (TN01); is relative of proband with type 1 diabetes
- Between ages 3-45 with normal Oral Glucose Tolerance Test (OGTT) or between ages 3-7 with an abnormal OGTT
- Confirmed positive for insulin autoantibodies within previous six months
- Confirmed positive for one or more other autoantibodies on two separate occasions within the past six months
Who cannot join
- Diagnosed with type 1 diabetes
- History of treatment with insulin or oral hypoglycemic agent
- History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months
- Ongoing use of medications known to influence glucose tolerance
- Pregnant or intending to become pregnant while on study or lactating
Trial locations and contacts
19 sites in 4 countries.
19 sites in 4 countries
United States16 sites
Emory Children's Center
Atlanta, Georgia, 30322
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, 80109
Joslin Diabetes Center
Boston, Massachusetts, 02215
University of Chicago
Chicago, Illinois, 60637
University of Texas Southwestern
Dallas, Texas, 75390
University of Florida
Gainesville, Florida, 32610
Baylor College of Medicine
Houston, Texas, 77030
Indiana University-Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Miami
Miami, Florida, 33136
Vanderbilt University
Nashville, Tennessee, 37232
Columbia University-Naomi Berrie Diabetes Center
New York, New York, 10032
University of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of California - San Francisco
San Francisco, California, 94158-2549
Benaroya Research Institute
Seattle, Washington, 98101
Stanford University
Stanford, California, 94305
University of South Florida
Tampa, Florida, 33612
Australia1 site
Walter and Eliza Hall Institute of Medical Research
Parkville, Victoria, 3050
About this study
Official title: Exploring Immunologic Effects of Oral Insulin in Relatives at Risk for Type 1
The study is a 2 arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D).
Read the detailed description
A minimum of 40 eligible participants will be identified for study participation from the TrialNet Pathway to Prevention study. Participants must have a relative with type 1 diabetes and be positive for insulin autoantibodies and at least one other autoantibody. All participants will receive active treatment of recombinant insulin treatment in capsules of either 67.5 mg daily or 500mg every other week. Participants will need to visit the study site up to eleven times over one year for blood tests and other study procedures. During the beginning treatment phase there are two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500mg treatment group. There are three additional treatment visits at months 2, 3, and 6 and 4 additional visits for follow-up at months 7, 8, 9 and 12. The primary outcome is the change in immune function as assessed by change in level or quality of T lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to baseline. .
- Conditions
- Type 1 Diabetes
- Being tested
- 67.5 mg oral insulin crystals daily, 500mg oral insulin crystals every other week
- Keywords
- oral insulin
- 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.
67.5 mg oral insulin crystals dailyDrug
Also called Humulin R crystals
human insulin crystals in capsules
500mg oral insulin crystals every other weekDrug
Also called Humulin R crystals
human insulin crystals in capsules
| Study group | Role | What they receive |
|---|---|---|
| 67.5 mg oral insulin crystals daily | Experimental | 67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months Receives: Drug: 67.5 mg oral insulin crystals daily |
| 500mg oral insulin crystals every other week | Experimental | 500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months Receives: Drug: 500mg oral insulin crystals every other week |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in GAD65 Autoantibody Titer (DK Units/mL)
Change in T-lymphocyte (GAD65) biomarker of beta cell specific immune response
Measured: 13 and 26 weeks after first dose versus baseline
Change in mIAA Autoantibody Titer From Baseline
Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response
Measured: 13 and 26 weeks after first dose versus baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study startJan 2016
- Primary completionMar 2018
- Study completionMar 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 (3)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Type 1 Diabetes TrialNet
- Responsible party
- Sponsor
- Investigators
- Carla Greenbaum, MD, Study chair, Type 1 Diabetes TrialNet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02580877
- Sponsor's protocol ID
- Oral Insulin-TN20
- Other IDs
- UC4DK106993, UC4DK117009
- Status last verified
- Jul 2020
- First submitted
- 30 Sep 2015
- Last updated
- 27 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data will be available at the NIDDK Central Repository
Publications
Skyler JS, Krischer JP, Wolfsdorf J, Cowie C, Palmer JP, Greenbaum C, Cuthbertson D, Rafkin-Mervis LE, Chase HP, Leschek E. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1. Diabetes Care. 2005 May;28(5):1068-76. doi: 10.2337/diacare.28.5.1068.
PubMed 15855569Bonifacio E, Ziegler AG, Klingensmith G, Schober E, Bingley PJ, Rottenkolber M, Theil A, Eugster A, Puff R, Peplow C, Buettner F, Lange K, Hasford J, Achenbach P; Pre-POINT Study Group. Effects of high-dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA. 2015 Apr 21;313(15):1541-9. doi: 10.1001/jama.2015.2928.
PubMed 25898052Jacobsen LM, Schatz DA. Insulin immunotherapy for pretype 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):390-396. doi: 10.1097/MED.0000000000000648.
PubMed 34091488
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring Immunologic Effects of Oral Insulin in Relatives at Risk for Type 1
- ClinicalTrials.gov ID
- NCT02580877
- Acronym / sponsor ID
- Oral Insulin-TN20
- Conditions
- Type 1 Diabetes
- Keywords
- oral insulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- Type 1 Diabetes TrialNet
- Study start
- Jan 2016
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 20 Oct 2015 (estimated)
- Results
- Posted 27 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a 2 arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D).
Detailed description
A minimum of 40 eligible participants will be identified for study participation from the TrialNet Pathway to Prevention study. Participants must have a relative with type 1 diabetes and be positive for insulin autoantibodies and at least one other autoantibody. All participants will receive active treatment of recombinant insulin treatment in capsules of either 67.5 mg daily or 500mg every other week. Participants will need to visit the study site up to eleven times over one year for blood tests and other study procedures. During the beginning treatment phase there are two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500mg treatment group. There are three additional treatment visits at months 2, 3, and 6 and 4 additional visits for follow-up at months 7, 8, 9 and 12. The primary outcome is the change in immune function as assessed by change in level or quality of T lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to baseline. .
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 67.5 mg oral insulin crystals daily | Experimental | Drug: 67.5 mg oral insulin crystals daily67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months |
| 500mg oral insulin crystals every other week | Experimental | Drug: 500mg oral insulin crystals every other week500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months |
Who may qualify
- Ages
- 3 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Participants in TrialNet Natural History/Pathway to Prevention Study (TN01); is relative of proband with type 1 diabetes
- Between ages 3-45 with normal Oral Glucose Tolerance Test (OGTT) or between ages 3-7 with an abnormal OGTT
- Confirmed positive for insulin autoantibodies within previous six months
- Confirmed positive for one or more other autoantibodies on two separate occasions within the past six months
Key exclusion criteria (5 listed)
- Diagnosed with type 1 diabetes
- History of treatment with insulin or oral hypoglycemic agent
- History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months
- Ongoing use of medications known to influence glucose tolerance
- Pregnant or intending to become pregnant while on study or lactating
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 |
|---|---|---|
| 67.5 mg oral insulin crystals dailyAlso: Humulin R crystalshuman insulin crystals in capsules | Drug | 67.5 mg oral insulin crystals daily |
| 500mg oral insulin crystals every other weekAlso: Humulin R crystalshuman insulin crystals in capsules | Drug | 500mg oral insulin crystals every other week |
Primary outcome
Change in GAD65 Autoantibody Titer (DK Units/mL)
Time frame: 13 and 26 weeks after first dose versus baseline
Change in T-lymphocyte (GAD65) biomarker of beta cell specific immune response
Change in mIAA Autoantibody Titer From Baseline
Time frame: 13 and 26 weeks after first dose versus baseline
Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15855569Skyler JS, Krischer JP, Wolfsdorf J, Cowie C, Palmer JP, Greenbaum C, Cuthbertson D, Rafkin-Mervis LE, Chase HP, Leschek E. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1. Diabetes Care. 2005 May;28(5):1068-76. doi: 10.2337/diacare.28.5.1068.
- Background: PubMed 25898052Bonifacio E, Ziegler AG, Klingensmith G, Schober E, Bingley PJ, Rottenkolber M, Theil A, Eugster A, Puff R, Peplow C, Buettner F, Lange K, Hasford J, Achenbach P; Pre-POINT Study Group. Effects of high-dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA. 2015 Apr 21;313(15):1541-9. doi: 10.1001/jama.2015.2928.
- Derived from this study: PubMed 34091488Jacobsen LM, Schatz DA. Insulin immunotherapy for pretype 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):390-396. doi: 10.1097/MED.0000000000000648.
- Individual participant dataSharing planned: Yes. Data will be available at the NIDDK Central Repository
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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.
Carla Greenbaum, MD study chair
Type 1 Diabetes TrialNet
19 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 67.5 mg oral insulin crystals daily and 500mg oral insulin crystals every other week in people with Type 1 Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 19 sites in 4 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 5 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 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Australia, Canada, Italy. 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?
Yes. Results are posted in the registry (first posted 27 Jul 2020). 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?
Change in GAD65 Autoantibody Titer (DK Units/mL) (time frame: 13 and 26 weeks after first dose versus baseline). 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?
On the ClinicalTrials.gov record for NCT02580877, which also lists 3 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 27 Jul 2020.