NCT00006505

Solitary Islet Transplantation for Type 1 Diabetes Mellitus Using Steroid Sparing Immunosuppression

Completed Phase 2 Last updated 20 April 2021

What this trial tests

Phase 2 trial testing Islet Transplantation in Diabetes Mellitus Type 1 in 6 participants. Completed in 21 April 2020.

Timeline

16 November 2000

Primary endpoint
30 June 2002

21 April 2020

Quick facts

Lead sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	6
Start date	16 November 2000
Primary completion	30 June 2002
Estimated completion	21 April 2020
Sites	1 location across United States

Drugs / interventions tested

• Islet Transplantation — full drug profile →

Conditions studied

• Diabetes Mellitus Type 1 — all drugs for Diabetes Mellitus Type 1 →

Sponsor

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

Who can join

Adults 18 to 65, any sex, with Diabetes Mellitus Type 1. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will test whether a new islet transplant procedure will enable patients with type 1 diabetes mellitus to stop insulin therapy. Islets are cell clusters in the pancreas that contain insulin-producing cells. The new procedure features three important advances, first developed by a group in Edmonton, Canada, over the way islet transplants have traditionally been performed: 1) the islets are transplanted immediately after they are removed from the donor; 2) islets are transplanted from two different donors in order to obtain the number of islets in a normal pancreas; and 3) the anti-rejection drug regimen is designed to reduce the harmful side effects of "conditioning" chemotherapy. (In the standard transplant procedure, patients receive intensive chemotherapy following the transplant. This study will use no radiation and lower-dose chemotherapy.)

Patients between the ages of 18 and 65 with the diagnosis of type 1 diabetes mellitus for at least 5 years may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, chest X-ray and tuberculin skin test, electrocardiogram and exercise test for heart function, abdominal ultrasound, psychological evaluation, and an arginine stimulated c-peptide test. The latter test determines if the patient is producing any insulin. Eligibility is restricted to patients who make no insulin at all.

The study has an active phase lasting 15 months and follow-up that continues indefinitely. Patients will receive 10,000 "islet equivalents" per kilogram (2.2 pounds) of body weight. This will likely require two separate transplant procedures from two donors. Before the first surgery, patients will be given anti-rejection (immune suppressing) drugs, including FK506 and rapamycin (orally) and daclizumab (intravenously). The islets will be infused through a tube placed in the portal vein (the large vein that feeds the liver). After surgery, patients will receive insulin intravenously for 24 hours. They will then have an abdominal ultrasound and blood tests to determine liver function. If fewer than 10,000 islets were transplanted, patients will continue insulin treatment, with the dosages adjusted to account for the transplanted islets. They will take Daclizumab every 2 weeks, and FK506 and rapamycin daily. Blood tests to follow how much of these drugs are in the blood stream will be performed daily at first and then weekly after blood levels of these drugs stabilize. They will be given antibiotics to prevent infections. The arginine test will be repeated 2 weeks after the transplant and periodically thereafter. Blood will be drawn weekly to check drug levels, and monthly for other tests. The investigators will track daily insulin requirements, and these will be recorded monthly.

Patients who require a second transplant to achieve the required amount of islets will return for the procedure when a compatible organ is donated. The second procedure will be done as described above. As before, insulin will be infused for 24 hours following surgery. It will then be stopped, however, and will not be resumed unless blood glucose levels reach above 180 milligrams/deciliter. Patients will continue taking FK506 and rapamycin indefinitely. Daclizumab will be given every 2 weeks for 4 doses following the second transplant, and then stopped. Patients will take an antiviral called ganciclovir for 14 weeks and another antibiotic for 1 year following surgery. For the first year after surgery, patients will have frequent blood tests to monitor drug levels and immune function. They will return to NIH for a complete history and physical examination 2 and 3 years after the final islet transplant and will be contacted yearly by phone to ascertain their general health status and whether they remain insulin independent.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Significant human beta-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating.
   Perl S, Kushner JA, Buchholz BA, Meeker AK, et al · · 2010 · cited 192× · PMID 20660050 · DOI 10.1210/jc.2010-0932
2. Pancreatic beta cell function persists in many patients with chronic type 1 diabetes, but is not dramatically improved by prolonged immunosuppression and euglycaemia from a beta cell allograft.
   Liu EH, Digon BJ, Hirshberg B, Chang R, et al · · 2009 · cited 46× · PMID 19418039 · DOI 10.1007/s00125-009-1342-7
3. Long-term immunosuppression after solitary islet transplantation is associated with preserved C-peptide secretion for more than a decade.
   Blau JE, Abegg MR, Flegel WA, Zhao X, et al · · 2015 · cited 12× · PMID 26184712 · DOI 10.1111/ajt.13383