Type 1 Diabetes
Conditions
Keywords
diabetes, HGB A1C, Beta Cell Regeneration
Brief summary
Sanford Research/USD proposes to study the combination therapy of oral administration of sitagliptin and lansoprazole versus placebo for the preservation of pancreatic beta cells still present in patients with recent-onset diabetes and possibly regenerating their beta cells, while safely down-regulating the autoimmune response directed against the beta cells.
Interventions
DRUGSitagliptin and Lansoprazole
Sitagliptin (dispensed as 50 mg capsules)and Lansoprazole(dispensed as 30 mg capsules) or matching placebo * Subjects age 11-17 years at Visit 2 will take 1 capsule once daily * Subjects age 18-45 years at Visit 2 will take 2 capsules once daily
DRUGPlacebo
Sitagliptin 50mg and Lansoprazole 30 mg or matching placebo will be given daily for 12 months. Subjects age 11-17 at visit 2 will take 1 capsule daily; age 18-45 will take 2 capsules daily.
Sponsors
Juvenile Diabetes Research Foundation
Sanford Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
11 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of type 1 diabetes, based on American Diabetes Association criteria, recently diagnosed (within the 6 months before Screening) and confirmed by the presence of at least 1 diabetes related autoantibody (either glutamic acid decarboxylase \[GAD\], insulinoma-associated protein \[IA 2\], or insulin, the latter measured within 10 days after starting insulin therapy). * Male or female aged between 11 and 45 years, inclusive. * Able to swallow study capsules. * Willing to comply with intensive diabetes management as directed by the investigator, with the goal of maintaining blood glucose as close to American Diabetes Association recommendations as possible. * Willing to comply with the schedule of study visits and protocol requirements.
Exclusion criteria
* Use of a GLP 1R agonist or DPP 4 inhibitor within 1 month before enrollment. * Use of a PPI within 1 month before enrollment. * Use of an oral hypoglycemic agent within 1 month before enrollment or use of thiazolidinediones within 3 months before enrollment (although thiazolidinediones may be used \<7days before enrollment). * Females of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period. * Females who are pregnant or breastfeeding at the time of enrollment. * Subjects with any of the following conditions: * Renal insufficiency, defined as estimated glomerular filtration rate (GFR) less than 50 mL/min at Screening, calculated using the Modification of Diet in Renal Disease (MDRD) equation. * History of a serious hypersensitivity reaction to sitagliptin or lansoprazole, such as anaphylaxis or angioedema. * Severe hepatic insufficiency. * History of pancreatitis or gallbladder disease * Any significant medical condition, which in the opinion of the investigator or medical monitor would interfere with study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 Hour C-peptide AUC in Response to MMTT | Month 12 | Blood samples for C-peptide were collected at baseline (pre-meal) and 15, 30, 60, 90 and 120 minutes post-meal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2 Hour C-peptide AUC in Response to MMTT | Month 6 | Blood samples for C-peptide were collected at baseline (pre-meal) and 15, 30, 60, 90, and 120 minutes post-meal. |
Countries
United States
Participant flow
Recruitment details
Four centers screened 79 participants were screened between August 2010 and May 2012. Participants aged 11-36 years, diagnosed with type 1 diabetes within the past 6 months were recruited. 9 participants were not randomized as 7 were deemed ineligible and 2 were lost to follow-up.
Pre-assignment details
At a screening visit, participants underwent procedures to establish that all inclusion criteria were met and none of the exclusion criteria were met. All participants and if applicable, guardians provided written informed consent/assent at screening.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin and Lansoprazole Oral Sitagliptin (100 mg for those age 18 -45 years, 50 mg for those age 11-17 years) and Lansoprazole (60 mg for those 18-45 years, 30 mg for those age 11-17 years for 12 months. Participants were then followed for an additional 12 months. | 46 |
| Placebo Matching placebo will be given daily for 12 months. Participants were then followed for an additional 12 months. | 22 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Sitagliptin and Lansoprazole | Total | Placebo |
|---|---|---|---|
| 2 -hour C-peptide Area Under Curve Result in Response to Standardized Mixed Meal Tolerance Test | 656 pmol/L STANDARD_DEVIATION 385 | 686 pmol/L STANDARD_DEVIATION 413 | 747 pmol/L STANDARD_DEVIATION 468 |
| Age, Customized Age (years) | 15.5 years STANDARD_DEVIATION 5.1 | 16.2 years STANDARD_DEVIATION 5.8 | 17.6 years STANDARD_DEVIATION 6.9 |
| Days Post diagnosis | 102.8 Days STANDARD_DEVIATION 51.8 | 103.4 Days STANDARD_DEVIATION 51.7 | 104.7 Days STANDARD_DEVIATION 52.8 |
| GAD antibody positive | 42 participants | 64 participants | 22 participants |
| Glucose (mmol/L) | 10.61 mmol/L STANDARD_DEVIATION 3.35 | 10.56 mmol/L STANDARD_DEVIATION 3.35 | 10.47 mmol/L STANDARD_DEVIATION 3.43 |
| HbA1c (%) | 7.19 % STANDARD_DEVIATION 1.09 | 7.18 % STANDARD_DEVIATION 1.09 | 7.15 % STANDARD_DEVIATION 1.13 |
| HLA DR4 Allele only | 19 participants | 25 participants | 6 participants |
| HLA DR Allele - Both DR3 and DR4 | 14 participants | 20 participants | 6 participants |
| HLA DR Allele - DR3 only | 11 participants | 18 participants | 7 participants |
| HLA DR Allele - Neither DR3 nor DR4 | 2 participants | 5 participants | 3 participants |
| IDA-HbA1c (%) | 8.9 % STANDARD_DEVIATION 1.53 | 8.83 % STANDARD_DEVIATION 1.49 | 8.68 % STANDARD_DEVIATION 1.43 |
| Insulin use (units/kg per day) | 0.43 units/kg per day STANDARD_DEVIATION 0.22 | 0.41 units/kg per day STANDARD_DEVIATION 0.2 | 0.38 units/kg per day STANDARD_DEVIATION 0.17 |
| Sex: Female, Male Female | 19 Participants | 29 Participants | 10 Participants |
| Sex: Female, Male Male | 27 Participants | 39 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 46 | 21 / 22 |
| serious Total, serious adverse events | 2 / 46 | 1 / 22 |
Outcome results
Primary
2 Hour C-peptide AUC in Response to MMTT
Blood samples for C-peptide were collected at baseline (pre-meal) and 15, 30, 60, 90 and 120 minutes post-meal.
Time frame: Month 12
Population: Of the 70 subjects randomized, 58 completed treatment and analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin and Lansoprazole | 2 Hour C-peptide AUC in Response to MMTT | 358 pmol/L |
| Placebo | 2 Hour C-peptide AUC in Response to MMTT | 495 pmol/L |
p-value: 0.81ANCOVA
Secondary
2 Hour C-peptide AUC in Response to MMTT
Blood samples for C-peptide were collected at baseline (pre-meal) and 15, 30, 60, 90, and 120 minutes post-meal.
Time frame: Month 6
Population: Of the 70 subjects randomized, 58 completed treatment and analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin and Lansoprazole | 2 Hour C-peptide AUC in Response to MMTT | 485 pmol/L |
| Placebo | 2 Hour C-peptide AUC in Response to MMTT | 675 pmol/L |
p-value: 0.869ANCOVA