Anti-inflammatory Therapy to Improve Outcomes After TPIAT

• Register: ClinicalTrials.gov
• Last refreshed on: 21 August 2023
• Main ID: NCT02713997
• Date of registration: 29/02/2016
• Prospective Registration: Yes
• Primary sponsor: University of Minnesota
• Public title: Anti-inflammatory Therapy to Improve Outcomes After TPIAT
• Scientific title: Anti-inflammatory Therapy to Improve Outcomes in Patients With Chronic Pancreatitis Undergoing Total Pancreatectomy Islet Autotransplantation
• Date of first enrolment: December 2016
• Target sample size: 44
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02713997
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age 18- 68 years. .

2. Scheduled for total pancreatectomy and IAT at University of Minnesota (UM). All
patients who are approved for pancreatectomy and IAT at UM are reviewed by a
multi-disciplinary committee including surgeons, gastroenterologists specializing in
pancreatic disease, a pain specialist, psychologist, and endocrinologist to confirm
the diagnosis of chronic pancreatitis and candidate suitability for surgery.

3. Able to provide informed consent

Exclusion Criteria:

1. Pre-existing diagnosis of diabetes mellitus, fasting blood glucose >115 mg/dl, or
hemoglobin A1c level >6.0% because these are all evidence of inadequate beta-cell
mass.

2. Use of any of the following treatments in the 30 days prior to enrollment: insulin,
metformin, sulfonylureas, glinides, thiazolidinediones, Glucagon Like Peptide (GLP)-1
agonists, dipeptidyl peptidase (DPP-4) inhibitors, or amylin.

3. Immunoglobulin (IgA) deficiency (serum level <5 mg/dL), which has been associated with
hypersensitivity to alpha-1 antitrypsin.

4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)>2.5 times the upper
limit of normal (ULN). Bilirubin >ULN, unless due to benign diagnosis such as
Gilbert's.

5. Known history of human immunodeficiency virus (HIV) infection, hepatitis B (chronic),
or hepatitis C (chronic).

6. History of tuberculosis (TB) (latent or active disease), or positive TB skin test.

7. History of symptomatic fungal lung infection.

8. History of multiple sclerosis, transverse myelitis, Guillain Barre, or other suspected
demyelinating disease, due to risk of exacerbation of these conditions with use of
etanercept; or prior history of systemic lupus erythematosus

9. Any of the following hematologic abnormalities: severe anemia (hgb <10 g/dL),
thrombocytopenia (<150/mm3), or neutropenia (<1.0 x109/L).

10. Current use or expected use of oral or injected corticosteroids, or any mediation
likely to affect glucose tolerance. However, use of hydrocortisone for physiologic
replacement, or use of any topical, inhaled, or intranasal glucocorticoid is
permitted.

11. Current or expected use of any other immunosuppressive agent.

12. Known hypersensitivity to etanercept or A1AT.

13. Any condition that is likely, in the opinion of the patient's medical providers, to
necessitate use of TNF alpha therapeutically in the future (such as psoriatic
arthritis).

14. Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin,
enoxaparin), or any history of pulmonary embolism.

15. For females, plans to become pregnant or unwillingness to use birth control for the
study duration.

16. Inability to comply with the study protocol.

17. Untreated psychiatric illness that may interfere with ability to give informed
consent, or other developmental delay or neurocognitive disorder that impairs with a
patient's ability to consent on their own behalf.

18. Any other medical condition that, in the opinion of the investigator, may interfere
with the patient's ability to successfully and safely complete the trial.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pancreatitis, Chronic; Diabetes; Transplant

Intervention(s)

Drug: Alpha 1-Antitrypsin

Drug: etanercept

Primary Outcome(s)

Maximal acute C-peptide response to glucose (ACRmax) [Time Frame: day 90]

Secondary Outcome(s)

area under the curve (AUC) C-peptide [Time Frame: day 90, 1 year, 2 years]

insulin independence [Time Frame: 1 year, 2 year]

maximal acute insulin response to glucose (AIRmax) [Time Frame: day 90, 1 year, 2 year]

Severe Adverse Events [Time Frame: cumulative, through 2 year visit]

insulin dose (unit/day) [Time Frame: day 90, 1 year, 2 years]

absence of severe hypoglycemia (SHE) with A1c <7% [Time Frame: 1 year, 2 years]

AUC glucose [Time Frame: day 90, 1 year, 2 years]

ACRmax [Time Frame: 1 year, 2 year]

Secondary ID(s)

PEDS-2016-22934

R01DK109914

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)