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Evaluation of the Efficacy of Intramuscular Islet Autograft After Extensive Pancreatectomy (AUTOGRAFTIM)

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ClinicalTrials.gov Identifier: NCT02872571
Recruitment Status : Recruiting
First Posted : August 19, 2016
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

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.

Condition or disease Intervention/treatment Phase
Disorder of Endocrine Pancreas Drug: Intramuscular Islet Autograft Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Evaluation of the Efficacy of Intramuscular Islet Autograft After Extensive Pancreatectomy
Actual Study Start Date : April 2013
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022

Arm Intervention/treatment
Experimental: Intramuscular Islet Autograft
Intramuscular Islet Autograft After Extensive Pancreatectomy
Drug: Intramuscular Islet Autograft
Intramuscular Islet Autograft After Extensive Pancreatectomy




Primary Outcome Measures :
  1. the percentage of patients with a functioning graft in the arm 3 months after autograft. [ Time Frame: 3 months ]
    Graft function will be estimated by the difference in insulin response between the two arms after the test stimulus by arginine (Acute Insulin Response or AIRarg) .The graft will be considered functional (success) when the insulin response in the grafted arm will be at least 30% higher compared to the other arm, 3 months after transplantation.


Secondary Outcome Measures :
  1. The percentage of patients with a functioning graft in the arm [ Time Frame: 6 months, 12 months ]
    To demonstrate the function of transplanted islets in the arm in patients receiving autologous islet intramuscularly after undergoing pancreatectomy for benign lesion extent, to prevent post surgical diabetes.

  2. Continuous Glucose Monitoring System [ Time Frame: at baseline ( before autograft) at 3,6,12 months ]
    Continuous recording of blood glucose during 72 hours by Continuous Glucose Monitoring System

  3. Oral Glucose Tolerance Test [ Time Frame: at baseline ( before autograft) at 3,6,12 months ]
    The glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood.

  4. hemoglobin A1c (HbA1c) blood test [ Time Frame: at baseline ( before autograft) at 3,6,12 months ]
    HbA1c measures blood glucose levels over a period of time.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02872571


Contacts
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Contact: François Pattou, MD,PhD fpattou@univ-lille2.fr
Contact: Violetta Raverdy, MD vraverdi@univ-lille2.fr

Locations
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France
Chu Amiens Picardie Recruiting
Amiens, France
CHRU, Hôpital Claude Huriez Recruiting
Lille, France
Principal Investigator: François Pattou, MD,PhD         
Institut Paoli Calmettes Recruiting
Marseille, France
CHU Rouen Recruiting
Rouen, France
Sponsors and Collaborators
University Hospital, Lille
Investigators
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Principal Investigator: François Pattou, MD, PhD University Hospital, Lille
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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02872571    
Other Study ID Numbers: 2010_49
2012-A00312-41 ( Other Identifier: ID-RCB number, ANSM )
First Posted: August 19, 2016    Key Record Dates
Last Update Posted: September 11, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University Hospital, Lille:
islet of Langerhans
transplantation
muscle