Chronic Pancreatitis
Conditions
Keywords
Islet autotransplantation, Alpha1 anti trypsin
Brief summary
Primary objective: To describe and compare the safety and efficacy of treatment with AAT in chronic pancreatitis patients who undergo total pancreatectomy and islet autotransplantation (TP-IAT).
Detailed description
The goal of this study is to assess whether infusion of Prolastin-C during peri-transplant period can enhance islet autograft survival and function in chronic pancreatitis patients who have total pancreatectomy and islet autotransplantation. This is a prospective, controlled, double-blind study. The primary endpoint will be area under the curve for the serum C-peptide level during the first 4 hours of an mixed meal tolerance test (MMTT), normalized by the number of islet equivalents (IEQ)/kg at day 365±14 after the transplant.
Interventions
DRUGProlastin-C
Patients will receive Prolastin-C at 60mg/kg on day 0, 7, 14, and 21 days of transplantation
DRUGPlacebo
Patients will receive saline on day 0, 7, 14, and 21 days of transplantation
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients scheduled for total pancreatectomy and islet auto-transplantation * Age \> 18 years * Diabetes free before surgery
Exclusion criteria
* Patients who are under immunosuppression * Patients who have had Puestow or Frey pancreatic surgery * Patients who have Immunoglobulin A (IgA) deficiency, known antibodies against IgA, or individuals with a history of severe immediate hypersensitivity reactions, including anaphylaxis to Alpha1-proteinase inhibitor products (allergic to AAT)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Islet Graft Function | 365 days | Islet graft function will be measured by 4 hour mixed meal tolerance test (MMTT) at 365 days post transplantation. Specific measurement is the C-peptide area under the curve (AUC) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prolastin-C Subjects will be given Prolastin-C intravenously at 60mg/kg weekly for 4 weeks.
Prolastin-C: Patients will receive Prolastin-C at 60mg/kg on day 0, 7, 14, and 21 days of transplantation | 29 |
| Placebo Subjects will be given Saline weekly for 4 weeks.
Placebo: Patients will receive saline on day 0, 7, 14, and 21 days of transplantation | 14 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Prolastin-C | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 14 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 13 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 14 Participants | 40 Participants |
| Region of Enrollment United States | 29 participants | 14 participants | 43 participants |
| Sex: Female, Male Female | 18 Participants | 10 Participants | 28 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 29 | 0 / 14 |
| other Total, other adverse events | 15 / 29 | 6 / 14 |
| serious Total, serious adverse events | 22 / 29 | 8 / 14 |
Outcome results
Primary
Islet Graft Function
Islet graft function will be measured by 4 hour mixed meal tolerance test (MMTT) at 365 days post transplantation. Specific measurement is the C-peptide area under the curve (AUC)
Time frame: 365 days
Population: All consented participants who received TPIAT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prolastin-C | Islet Graft Function | 233 ng/ml*min | Standard Error 42 |
| Placebo | Islet Graft Function | 354 ng/ml*min | Standard Error 78 |