Islet transplantation for patients with brittle Type 1 diabetes

Islet Transplantation in Patients With "Brittle" Type I Diabetes

This study is testing whether islet transplantation can help people with brittle Type 1 diabetes manage their blood sugar better without needing insulin shots.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: University of Chicago (other)
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT01630850 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety of islet transplantation in patients with brittle Type 1 diabetes mellitus, which may help achieve better blood sugar control without the need for insulin injections. The procedure involves obtaining islet cells from deceased donors and infusing them into the patients' bodies through a vein. Participants will be closely monitored to assess the effectiveness and safety of this intervention.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a long history of insulin-dependent Type 1 diabetes and severe hypoglycemia episodes.

Not a fit: Patients who do not have a history of severe hypoglycemia or those with Type 2 diabetes will likely not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve blood sugar management and quality of life for patients with brittle Type 1 diabetes.

How similar studies have performed: Previous studies on islet transplantation have shown promising results, indicating that this approach has potential benefits for similar patient populations.

Eligibility criteria

Inclusion Criteria:

* Male and female patients 18 to 70 years of age.
* Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
* Clinical history compatible with T1D with onset of disease at \< 40 years of age, insulin-dependence for ≥ 5 years at the time of enrollment, and a sum of patient age and insulin dependent diabetes duration of ≥ 28 and absent stimulated c-peptide (\<0.3ng/mL) in response to a mixed meal tolerance test (MMTT; Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost) measured at 60 and 90 min after the start of consumption and at least one episode of severe hypoglycemia in the 12 months prior to study enrollment; OR a clinical history of "problematic hypoglycemia" defined as defined as two or more episodes per year of severe hypoglycemia or as one episode associated with impaired awareness of hypoglycemia, extreme glycemic lability, or major fear and maladaptive behavior according to recent clinical recommendations.
* Involvement in intensive diabetes management defined as self monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the 12 months prior to study enrollment.
* Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR a HYPO score greater than or equal to the 90th percentile (1047) during the screening period and within the last 6 months; OR marked glycemic lability characterized by wide swings in blood glucose despite optimal diabetes therapy and defined by an LI score greater than or equal to the 90th percentile (433 mmol/L2/h -wk1) during the screening period and within the last 6 months prior to randomization; OR a composite of a Clarke score of 4 or more and a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) during the screening period and within the last 6 months.

Exclusion Criteria:

* Body mass index (BMI) \>30 kg/m2 or patient weight \<50kg.
* Insulin requirement \>1.0 IU/kg/day or \<15 U/day.
* Untreated proliferative diabetic retinopathy.
* Blood Pressure: SBP \>160 mmHg or DBP \>100 mmHg.
* Measured glomerular filtration rate \<80 mL/min/1.73m2 (using iohexol or calculated using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation) or based on 24-hrs urine collection. Strict vegetarians (vegans) with a calculated GFR \<70 mL/min/1.73m2 are excluded. The absolute (raw) GFR value will be used for subjects with body surface areas \>1.73 m2.
* Presence or history of macroalbuminuria (\>300 mg/g creatinine).
* Presence or history of panel-reactive anti-HLA antibodies above 30% or history/presence of donor specific anti-HLA antibodies in order to avoid unacceptable antigen(s) (Campbell PM 2007).
* For female subjects: Positive pregnancy test, presently breast-feeding, wishes to be pregnant at any time point in the future, which includes during or after the completion of the study even if study participation is ended early, 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.
* Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
* Known active alcohol or substance abuse.
* Severe co-existing cardiac disease
* Known hypercoagulative state.
* Symptomatic cholecystolithiasis.
* Acute or chronic pancreatitis.

Other protocol related inclusion/exclusion criteria may apply.

Where this trial is running

Chicago, Illinois

• University of Chicago Medical Center — Chicago, Illinois, United States (RECRUITING)

Study contacts

• Principal investigator: Piotr Witkowski, MD, PhD — University of Chicago
• Study coordinator: Lindsay Basto, RN, BSN

Conditions: Diabetes Mellitus, Type 1