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Diabetes Mellitus, Type 1Phase 1NCT02402439

Treatment of Type I Diabetes by Islet Transplantation Into the Gastric Submucosa Study Protocol

A Phase 1 study testing Islet cells and Islet transplantation into the gastrointestinal submucosa in people with Diabetes Mellitus, Type 1, run by Chuck Rickert, MD, PhD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this trial is to gain initial clinical experience regarding the safety and efficacy of treating type I diabetes in people who have received a kidney transplant by transplanting islets into a new transplant site in the stomach (gastrointestinal submucosa). Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Islet cells and Islet transplantation into the gastrointestinal submucosa
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Mar 2016to 30 Apr 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female subjects age 18 to 70 years of age.
  • Subjects who are able to provide written informed consent and to comply with study procedures.
  • Clinical history compatible with T1D (onset < 40 yrs old and insulin dependent for > 5 yrs at enrollment.
  • Absent stimulated c-peptide (< 0.3 ng/mL) in response to a (Boost® 6 mL/kg BW to a maximum of 360 mL; another equivalent product), measured at 60 and 90 min after start of consumption.
  • Subjects who are > 3 months post-renal transplant who are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppression ([tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic, or azathioprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic ± Prednisone ≤ 10 mg/day).
  • Stable renal function as defined by a creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplant, until rejection, obstruction or infection is ruled out.
  • Reduced awareness of hypoglycemia manifested a Clarke score >4 and at least 1 episode of severe hypoglycemia in the past 12 months prior to study enrollment. This criterion requires that there has been involvement in intensive diabetes management under the direction of an endocrinologist, diabetologist, or diabetes specialist prior to study enrollment. Intensive diabetes management is defined as self-monitoring of glucose values no less than 3 times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Severe hypoglycemia is defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, and which was associated with either a BG level < 54 mg/dl [3.0 mmol/L] or prompt recovery after oral carbohydrate, IV glucose, or glucagon administration.

Who cannot join

  • Weight more than 100 kg or body mass index (BMI) > 30 kg/m2.
  • Insulin requirement of >1.0 IU/kg/day or <15 U/day.
  • Other (non-kidney) organ transplants except prior failed pancreatic graft where graft failure is attributed to thrombosis within the first 4 weeks or to other technical reasons that require graft pancreatectomy; with the graft pancreatectomy occurring more than 6 months prior to enrollment.
  • Untreated or unstable proliferative diabetic retinopathy.
  • Blood Pressure: SBP > 160 mmHg or DBP >100 mmHg despite treatment with antihypertensive agents.
  • Calculated GFR of ≤ 40 mL/min/1.73 m2 using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. (59)
Show all 32Show fewer
  • Proteinuria (albumin/creatinine ratio or ACr > 300mg/g) of new onset since kidney transplantation.
  • Calculated panel-reactive anti-HLA antibodies > 50%. Subjects with calculated panel reactive anti-HLA antibodies ≤ 50% will be excluded if any of the following are detected:
  • Positive cross-match
  • Islet donor-directed anti-HLA antibodies detected by Luminex® Single Antigen/specificity bead assay including weakly reactive antibodies that would not be detected by a flow cross-match
  • For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
  • Active infection including hepatitis B, hepatitis C, HIV, or TB. A positive skin test (PPD) in itself is not an exclusion, and will be followed up by a QuantiFERON® gold assay.
  • Negative screen for EBV IgG.
  • Invasive Aspergillus, Histoplasmosis, and Coccidioidomycosis infection within 1 year prior to study entry.
  • Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
  • Known active alcohol or substance abuse.
  • Severe co-existing cardiac disease, characterized by any one of these conditions:
  • Recent MI (within past 6 months),
  • Evidence of ischemia on functional cardiac exam within the last year,
  • Left ventricular ejection fraction < 30%,
  • Valvular disease requiring replacement with prosthetic valve.
  • Persistent elevation of liver function tests at time of study entry. Persistent SGOT (AST), SGPT (ALT), alkaline phosphatase values > 1.5, or total bilirubin > 1 times normal upper limits will exclude a subject.
  • Active infections (except mild skin and nail fungal infections).
  • Acute or chronic pancreatitis.
  • Active peptic ulcer disease or gastritis, symptomatic gallstones, or portal hypertension.
  • Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
  • Use of any investigational agents within 4 weeks of enrollment.
  • Administration of live attenuated vaccine(s) within 2 months of enrollment.
  • Any medical condition that, in the opinion of the investigator, will interfere with safe study completion.
  • Positive screen for BK viremia at time of screening.
  • Untreated hyperlipidemia - TC > 200 mg/dL, TGC > 200 mg/dL, LDL > 130 mg/dL
  • Use of glucocorticoids for non-transplant-related indications.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94143-0780

Other trials in United States

About this study

The goal of this trial is to gain initial clinical experience regarding the safety and efficacy of treating type I diabetes in people who have received a kidney transplant by transplanting islets into a new transplant site in the stomach (gastrointestinal submucosa). A total of 6 patients will be enrolled in the study and followed for a period of up to 3 years after the last islet transplant.

Read the detailed description

Pancreatic islet transplantation offers a minimally invasive approach to restore normoglycemia in type 1 diabetics while avoiding the hypoglycemic complications observed with intensive insulin therapy and the surgical complications associated with pancreas transplantation. Although significant progress has been made in clinical islet transplantation, overall outcomes remain suboptimal since many patients lose insulin independence a few years after transplantation and multiple donors are usually needed to achieve independence. The cause of this progressive loss of function is multifactorial, but mounting evidence suggests that much of the islet loss after transplant is directly related to the intraportal transplant site that is used in clinical islet transplantation. Intravascular infusion of the islets triggers a severe,non-specific inflammatory response (immediate blood-mediated inflammatory reaction, IBMIR) which destroys at least 50% of the islet mass. The engraftment of the surviving islets is further compromised by the relatively hypoxic portal venous environment, and the infused islets are exposed to potentially toxic levels of immunosuppressive agents being absorbed from the gut into the portal circulation. Together, these characteristics contribute to early as well as late loss of islet function after transplantation. The gastrointestinal submucosa is a newly described transplant site that can support islet engraftment while avoiding many of the drawbacks associated with intraportal infusion. In addition, this site is easily accessible via upper endoscopy and the submucosal injection procedure is safe and technically straightforward.

The aim of this prospective, single-center trial is to provide initial clinical experience regarding the safety and efficacy of endoscopic gastric and duodenal submucosal islet transplantation in type I diabetic patients with kidney allografts. A total of 6 patients will be recruited into the trial. The investigators will follow the standardized islet manufacturing protocols and the thymoglobulin-based induction immunosuppressive regimen developed by the Clinical Islet Transplant consortium (CIT). Outcomes will include safety measures, glycemic control and insulin use, metabolic assessments of graft function, allo/auto-immune responses, and protocol biopsies to assess graft rejection/inflammation. The investigators believe that this novel approach to islet transplantation has the potential to significantly improve current islet transplantation outcomes by enhancing islet engraftment and long-term function.

Being tested
Islet cells, Islet transplantation into the gastrointestinal submucosa
Keywords
Type 1 diabetes, diabetes mellitus, pancreatic islet transplant, beta cell replacement
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Islet cellsDrug

    Also called pancreas

    Transplantation of islets into the gastrointestinal submucosa

  • Islet transplantation into the gastrointestinal submucosaProcedure or surgery

    Also called pancreas

    Transplantation of islets into the gastrointestinal submucosa

Study groups in NCT02402439
Study groupRoleWhat they receive
Islet TransplantExperimentalIslet transplantation into the gastrointestinal submucosa
Receives: Drug: Islet cells; Procedure: Islet transplantation into the gastrointestinal submucosa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Insulin independence

    off insulin therapy for at least 1 week and all of the following criteria are met:

    • HbA1c < 6.5% or a > 2.5% decrease from baseline;
    • Daily fasting capillary glucose should not exceed 140 mg/dL (7.8 mmol/L) more than 3 times in the past week;
    • 2-hour post-prandial capillary glucose should not exceed 180 mg/dl (10.0 mmol/L) more than three times in the past week;
    • Fasting plasma glucose < 126 mg/dL (7.0 mmol/L); if the fasting plasma glucose is > 126 mg/dL (7.0 mmol/L), it must be confirmed in an additional one out of two measurements; Protocol Version 4.0 December 19, 2017 39
    • Evidence of endogenous insulin production defined as fasting or stimulated C-peptide >0.5 ng/mL (0.16 nmol/L).

    Measured: 75 days after the first transplant

  2. Insulin independence

    off insulin therapy for at least 1 week and all of the following criteria are met:

    • HbA1c < 6.5% or a > 2.5% decrease from baseline;
    • Daily fasting capillary glucose should not exceed 140 mg/dL (7.8 mmol/L) more than 3 times in the past week;
    • 2-hour post-prandial capillary glucose should not exceed 180 mg/dl (10.0 mmol/L) more than three times in the past week;
    • Fasting plasma glucose < 126 mg/dL (7.0 mmol/L); if the fasting plasma glucose is > 126 mg/dL (7.0 mmol/L), it must be confirmed in an additional one out of two measurements; Protocol Version 4.0 December 19, 2017 39
    • Evidence of endogenous insulin production defined as fasting or stimulated C-peptide >0.5 ng/mL (0.16 nmol/L).

    Measured: 1 year after the first transplant

  3. Insulin independence

    off insulin therapy for at least 1 week and all of the following criteria are met:

    • HbA1c < 6.5% or a > 2.5% decrease from baseline;
    • Daily fasting capillary glucose should not exceed 140 mg/dL (7.8 mmol/L) more than 3 times in the past week;
    • 2-hour post-prandial capillary glucose should not exceed 180 mg/dl (10.0 mmol/L) more than three times in the past week;
    • Fasting plasma glucose < 126 mg/dL (7.0 mmol/L); if the fasting plasma glucose is > 126 mg/dL (7.0 mmol/L), it must be confirmed in an additional one out of two measurements; Protocol Version 4.0 December 19, 2017 39
    • Evidence of endogenous insulin production defined as fasting or stimulated C-peptide >0.5 ng/mL (0.16 nmol/L).

    Measured: 1 year after the last transplant

Secondary outcomes (3)

  1. Changes in HbA1c

    Proportion of subjects with an HbA1c <7.0% and free of severe hypoglycemic events from day 28 to 365 after the first and final islet transplant

    Measured: From day 28 to 365

  2. Changes (reduction) in insulin requirements

    decrease of insulin dose as compared to pre-transplantation of islets

    Measured: up to 5 years

  3. Incidence of adverse events

    the incidence of AEs related to the transplant procedure or immunosuppression

    Measured: up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2015 (estimated)
  2. Study startMar 2016
  3. Primary completion30 Apr 2019
  4. Study completion30 Apr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02402439
Sponsor's protocol ID
IGS
Status last verified
Sep 2026
First submitted
18 Mar 2015
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Islet cells and Islet transplantation into the gastrointestinal submucosa in people with Diabetes Mellitus, Type 1, run by Chuck Rickert, MD, PhD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Insulin independence (time frame: 75 days after the first transplant). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02402439.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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