Improving Islet Transplantation Outcomes With Gastrin
| Status: | Recruiting |
|---|---|
| Conditions: | Diabetes, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 68 |
| Updated: | 3/7/2019 |
| Start Date: | February 1, 2019 |
| End Date: | December 2023 |
| Contact: | City of Hope Diabetes and Metabolism Research Institute |
| Email: | Islets@coh.org |
| Phone: | 1-866-44-ISLET(1-866-444-7538) |
This clinical study will evaluate the safety and effectiveness of Gastrin treatment with
islet transplantation to help patients with difficult to control type 1 diabetes make insulin
again and improve blood sugar control.
This study involves two investigational (experimental) products not yet approved by the U.S.
Food and Drug Administration (FDA) as a treatment for any disease:
1. Human allogenic islet cells (islet cells from a deceased, unrelated human donor)
2. Gastrin-17 (Gastrin) - a hormone secreted by the gut
Islet cell transplantation involves transplanting the cells that make insulin from a pancreas
of deceased organ donor to a patient with diabetes. Because there is a limited supply of
donor islet cells available, this study is testing whether Gastrin injections can help make a
fewer number of transplanted islets work better.
Gastrin is a natural gut hormone that is present in the pancreas during its development in
the embryo but not after birth, and is believed to participate in the formation of the normal
pancreas. Several studies have tried to use gastrin to help grow insulin making islet cells
in laboratory experiments or after transplanting islets in laboratory animals. In early
clinical trials, diabetic patients treated with gastrin and other growth factors required
less insulin after 4 weeks of gastrin treatment and the effect lasted more than 12 weeks
after stopping treatment, suggesting that gastrin may have increased the number of cells that
make insulin.
This study will evaluate whether taking Gastrin injections following a single islet
transplantation is safe, improves how well the islet transplant works and/or helps increase
the number of insulin-making cells in the islets.
Qualified participants will receive treatment with a single islet transplant, followed by two
rounds of gastrin treatment (twice daily injections for 30 days) just after transplant and
again 6 months later. Study participants will also take anti-rejection medications (to
prevent the body from rejecting the islet cells) and other medications to guard against
infection and support their health and/or the health of the transplanted islets. Participants
will need to return to City of Hope in Duarte, CA for frequent follow-up visits for one year
after transplant.
islet transplantation to help patients with difficult to control type 1 diabetes make insulin
again and improve blood sugar control.
This study involves two investigational (experimental) products not yet approved by the U.S.
Food and Drug Administration (FDA) as a treatment for any disease:
1. Human allogenic islet cells (islet cells from a deceased, unrelated human donor)
2. Gastrin-17 (Gastrin) - a hormone secreted by the gut
Islet cell transplantation involves transplanting the cells that make insulin from a pancreas
of deceased organ donor to a patient with diabetes. Because there is a limited supply of
donor islet cells available, this study is testing whether Gastrin injections can help make a
fewer number of transplanted islets work better.
Gastrin is a natural gut hormone that is present in the pancreas during its development in
the embryo but not after birth, and is believed to participate in the formation of the normal
pancreas. Several studies have tried to use gastrin to help grow insulin making islet cells
in laboratory experiments or after transplanting islets in laboratory animals. In early
clinical trials, diabetic patients treated with gastrin and other growth factors required
less insulin after 4 weeks of gastrin treatment and the effect lasted more than 12 weeks
after stopping treatment, suggesting that gastrin may have increased the number of cells that
make insulin.
This study will evaluate whether taking Gastrin injections following a single islet
transplantation is safe, improves how well the islet transplant works and/or helps increase
the number of insulin-making cells in the islets.
Qualified participants will receive treatment with a single islet transplant, followed by two
rounds of gastrin treatment (twice daily injections for 30 days) just after transplant and
again 6 months later. Study participants will also take anti-rejection medications (to
prevent the body from rejecting the islet cells) and other medications to guard against
infection and support their health and/or the health of the transplanted islets. Participants
will need to return to City of Hope in Duarte, CA for frequent follow-up visits for one year
after transplant.
Inclusion Criteria:
1. Age 18-68 years
2. Type 1 diabetes mellitus (documented with fasting C-peptide level of < 0.2 ng/ml
before and < 0.3 ng/ml after IV administration of 1 mg of glucagon) for at least 5
years.
3. Frequent hypoglycemia (blood glucose 54 mg/dl more than once per week) -or-
Hypoglycemia unawareness (Clarke score of 4 or more). -or- One or more severe
hypoglycemic episodes in 12 months preceding enrollment (see Section 3.1.4 for
definition)
4. Ability and willingness to comply with post-transplant regimen, including
immunosuppression, use of reliable contraception, frequent clinic visits, testing and
maintaining detailed logs of blood glucose levels, insulin doses and medications, and
completing detailed follow-up studies.
5. Ability to give informed consent.
Exclusion Criteria:
1. Weight > 80 kg or BMI > 30
2. Insulin requirements > 50 units/day
3. Known sensitization to rATG
4. Significant kidney disease (estimated GFR from serum creatinine measurement <70
ml/min, random spot urine microalbumin to creatinine ratio >300mg albumin/g
creatinine)
5. Significant hepatobiliary disease, including elevation of liver enzymes > twice the
upper limit of normal for each of ALT and AST (any elevation of these enzymes will be
determined), bilirubin not within normal limits, albumin < 3.5 g/dl, liver masses,
portal vein thrombosis, evidence of portal hypertension, or significant, untreated
gallbladder disease (i.e. gallstones)
6. Significant cardiovascular disease, including non-correctable coronary artery disease
with ejection fraction < 50% and/or recent myocardial infarction (within last 12
months); or extensive peripheral vascular disease not correctable by surgery,
7. Evidence of active proliferative retinopathy
8. Hypertension (140/90) despite appropriate treatment
9. Hyperlipidemia (total cholesterol > 260 mg/dl, LDL > 160 mg/dl, and/or triglycerides >
300 mg/dl) despite appropriate treatment
10. Anemia (Hgb < 11 g/dl) or other hematologic disorders that require medical attention
11. WBC <3,000/l
12. Increased risk of bleeding (platelet count < 120,000 cells/l; INR > 1.5), other
chronic hemostasis disorders, or treatment with chronic anticoagulant therapy (i.e.
heparin or warfarin)
13. Recent unresolved acute infection (except for mild skin infection or nail fungal
infection), or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or
syphilis (RPR)
14. EBV IgG negative
15. Any history of malignancy, except completely resected squamous or basal cell skin
cancer or in situ cancer of the cervix
16. Active peptic ulcer disease or current therapy with proton pump inhibitor (PPI)
17. Symptomatic gastroparesis
18. History of gastric bypass
19. Recent history of non-adherence to recommended medical therapy
20. Psychiatric illness that is untreated, or likely to interfere significantly with study
compliance despite treatment
21. Previous organ/tissue transplant
22. Presence of preformed antibodies on panel reactive antibody screening > 20%
23. Administration of live attenuated vaccines within 60 days of enrollment.
24. Presence of a chronic disease that must be chronically treated with contraindicated
medications
25. Use of investigational agents within four weeks of enrollment
26. Active alcohol or substance abuse, including cigarette smoking (must be abstinent for
> 3 months)
27. Pregnant women, women intending future pregnancy, women of reproductive potential who
are unable or unwilling to follow effective contraceptive measures (i.e., tubal
ligation, two barrier methods, abstinence) for the duration of study treatment and for
as long as they are on immunosuppressive medication, and women presently
breastfeeding.
28. Individuals without health insurance covering the cost of immunosuppression and
clinical and laboratory follow-up after completion of the study
29. Any medical condition that in the opinion of the investigator will interfere with safe
participation in the trial
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