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

NCT02402439 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: IGS
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Type 1 diabetes; diabetes mellitus; pancreatic islet transplant; beta cell replacement

Outcome Measures

Primary Outcomes (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).

  75 days after the first transplant

• 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).

  1 year after the first transplant

• 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).

  1 year after the last transplant

Secondary Outcomes (3)

• Changes in HbA1c

  From day 28 to 365

• Changes (reduction) in insulin requirements

  up to 5 years

• Incidence of adverse events

  up to 5 years

Study Arms (1)

Islet Transplant

EXPERIMENTAL

Islet transplantation into the gastrointestinal submucosa

Drug: Islet cells; Procedure: Islet transplantation into the gastrointestinal submucosa

Interventions

Islet cells DRUG

Transplantation of islets into the gastrointestinal submucosa

Also known as: pancreas

Islet Transplant

Islet transplantation into the gastrointestinal submucosa PROCEDURE

Transplantation of islets into the gastrointestinal submucosa

Also known as: pancreas

Islet Transplant

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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.
• 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.

Sponsors & Collaborators

• Andrew Posselt: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143-0780, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Pancreatic Hormones

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Andrew M Posselt, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery in Residence

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: March 30, 2015
• Study Start: March 1, 2016
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)