Clinical trial NCT02872571: Evaluation of the Efficacy of Intramuscular Islet Autograft After Extensive Pancreatectomy
Official title: Evaluation of the Efficacy of Intramuscular Islet Autograft After Extensive Pancreatectomy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Disorder of Endocrine Pancreas
Keywords: islet of Langerhans
transplantation
muscle
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2016-08-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The liver may not be an optimal site for islet transplantation due to obstacles by an instant blood-mediated inflammatory response, and low revascularization of transplanted islets. Therefore, intramuscular islet transplantation offers an attractive alternative, based on its simplicity, enabling easier access for noninvasive graft imaging and cell explantation.

Detailed description: The field of β cell replacement therapies has progressed extensively over the last decades. It is well established that successful intraportal islet transplantation can restore endogenous β cell function to subjects with type 1 diabetes mellitus. In fact, when the graft function is optimal, insulin independence can be consistently prolonged for up to 5 years in 50% of patients. Several factors influence the outcome and performance of the graft upon implantation. For instance, preclinical studies have confirmed the significant differences in utilizing several sites for the implantation of islet grafts, but the most utilized clinical approach is embolization into the liver. However, it has become evidently clear that the liver may not be the optimal environment as a recipient site for pancreatic islets, owing not only to immunologic, but also to anatomic and physiologic factors that may promote a decline in islet function. Moreover, intrahepatic islet infusion is often associated with an immediate blood- mediated inflammatory reaction , thrombosis and hepatic tissue ischemia with elevated blood liver enzymes. In addition, the cross-talk between activated coagulation and inflammatory mediators after implantation, dramatically affects islet cell survival and engraftment, resulting in β cell dysfunction or death, depicting primary nonfunction as a consequence of reduced functional islet mass. This intrahepatic environment appears to potently impair the metabolic functions of transplanted islets. Furthermore, the complications associated with graft recovery within the hepatic site, will further limit its potential applications in exploiting insulin-secreting cells obtained from alternative cell sources. These include xenogenic islets, immortalized β cell lines, embryonic stem cells, or adult progenitor cells, including β cell encapsulation.

Restoration of β cell function is a highly desirable goal for patients with unstable diabetes; therefore, the search for an alternative site that is safer for islet transplantation is imperative.

In man, autotransplantation of minced tissue into striated muscle following blunt dissection has been successfully used in parathyroid surgery for several decades. Initially demonstrated in rodents in the early 1980s, intramuscular islet transplantation (IMIT) has rarely been considered as a clinically feasible implantation site.

This study want to provide direct evidence of the feasibility and function of autologous islets transplanted in the muscle

Eligibility criteria: Inclusion Criteria:

age over 18 years indication for pancreatectomy for benign pancreatic disease not genetically determined (chronic pancreatitis, ductal lesions, neuroendocrine or cystic tumors) or pancreatic trauma

Exclusion Criteria:

Patients with suspected lesion genetically determined or malignant on the basis of preoperative and / or during surgical exploration and / or during pathological examination Refusal to sign the consent form Patient not affiliated with a social security scheme Pregnant or lactating women Persons deprived of liberty, person under guardianship

Primary outcomes:
measure: the percentage of patients with a functioning graft in the arm 3 months after autograft.
timeFrame: 3 months
Secondary outcomes:
measure: The percentage of patients with a functioning graft in the arm
timeFrame: 6 months, 12 months
measure: Continuous Glucose Monitoring System
timeFrame: at baseline ( before autograft) at 3,6,12 months
measure: Oral Glucose Tolerance Test
timeFrame: at baseline ( before autograft) at 3,6,12 months
measure: hemoglobin A1c (HbA1c) blood test
timeFrame: at baseline ( before autograft) at 3,6,12 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens Picardie
city: Lille
country: France
facility: CHRU, Hôpital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Rouen
country: France
facility: CHU Rouen
Study officials:
affiliation: University Hospital, Lille
name: François Pattou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: