Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001573842
Ethics application status
Approved
Date submitted
11/10/2021
Date registered
18/11/2021
Date last updated
31/10/2022
Date data sharing statement initially provided
18/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Islet transplant into the skin - a novel treatment for type 1 diabetes using organ donor islets and an integrated scaffold.
Scientific title
‘Intracutaneous ectopic pancreas’ - A prospective evaluation of a novel treatment for Type I Diabetes Mellitus employing deceased donor islets implanted into modified, pre-integrated Biodegradable Temporising Matrix (BTM) dermal replacement.
Secondary ID [1] 305509 0
None
Universal Trial Number (UTN)
Trial acronym
INCEPTR
INtraCutaneous Ectopic Pancreas Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 323901 0
Condition category
Condition code
Metabolic and Endocrine 321414 321414 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is prospective, non-controlled, pilot proof-of-concept study of safety and design property achievement. It is a combination of two clinically approved products; cadaveric islets - transplanted into the liver for treatment of hypoglycemic unaware type 1 diabetics with poorly controlled disease and the Biodegradable Temporizing Matrix (BTM) - a synthetic polymer approved for the treatment of full thickness burns.
In combination, the BTM is implanted into a surgically created wound (approximately 10X4cm elliptical wound) in the inter-biceps/triceps groove of the medial arm in the trial participant. Then following a period of integration (>17 days) cadaveric islets from a consented organ donor are transplanted into the newly created hypervascular site (an alternative to the intrahepatic site).
The wound creation and BTM implant will be performed by a burns sugeon (Royal Adelaide Hospital) who has many years experience performing similar surguries to treat full thickness burns using the BTM. It is anticipated this process will take less than a hour to complete.
The islet transplant process will take less than 1 hour to complete and will be performed by the Islet transplant scientist, who has over 10 years experience performing islet transplants within the Nationally Funded Centres - Islet transplant program at the Royal Adelaide Hospital.
Wound site and BTM integration will be monitored at dressing changes and photographed to document progress.
Intervention code [1] 321912 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329191 0
Detectable serum c-peptide (blood Test - analysis SA Pathology Clinical and Diagnostic Service)
Timepoint [1] 329191 0
Measured 3 months from islet transplant for each participant.
Secondary outcome [1] 401740 0
Exogenous insulin usage (total daily dose) - measured by patient diary/ or from patient pump data
Timepoint [1] 401740 0
Measured at baseline, 3, 6 and 12 months from islet transplant.
Secondary outcome [2] 401741 0
Quality of Life score - SF36 Questionnaire
Timepoint [2] 401741 0
Pre islet transplant, 3, 6 and 12 months post islet transplant.
Secondary outcome [3] 402534 0
Blood glucose control - Libre Freestyle monitoring (2 week continuous data collection) or CGMS
Timepoint [3] 402534 0
Measured at baseline, 3, 6 and 12 months from islet transplant.
Secondary outcome [4] 402535 0
HbA1c - (blood Test - analysis SA Pathology Clinical and Diagnostic Service)
Timepoint [4] 402535 0
Measured at baseline, 3, 6 and 12 months from islet transplant.

Eligibility
Key inclusion criteria
Patients with Type 1 Diabetes Mellitus who are recipients of a functional renal allograft (glomerular filtration rate of >40 ml/min) and taking immunosuppressant medication following that allograft.
Minimum age
50 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnancy/Lactation
Active infection or malignancy (other than locally controlled squamous cell carcinoma or basal cell carcinoma)
Non-English speakers (from an informed consent perspective), unless an information and consent form in the subject’s language is available along with a study coordinator capable of answering questions in that language.
Known allergy/previous reaction to polyurethane dressing materials
Unwillingness to consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a pilot study and the recruitment number is small (5). However, some statistical significance may be produced and will be determined by analysis of variance (ANOVA), multiple logistic regression analysis, and by independent t-tests corrected for the numbers of comparisons, as appropriate for the data set. The two-sided probability level of 0.05 will be used as the criterion for significance.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/12/2021
Actual
31/03/2022
Date of last participant enrolment
Anticipated
31/12/2022
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
5
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 20712 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 35513 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 309875 0
Charities/Societies/Foundations
Name [1] 309875 0
Juvenile Diabetes Research Foundation Australia
Country [1] 309875 0
Australia
Funding source category [2] 309876 0
Charities/Societies/Foundations
Name [2] 309876 0
Juvenile Diabetes Research Foundation International
Country [2] 309876 0
United States of America
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
1 Port Road
Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 310907 0
None
Name [1] 310907 0
Address [1] 310907 0
Country [1] 310907 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309605 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 309605 0
Central Adelaide Local Health Network Inc.
SA Health
Level 3, Roma Mitchell Building
136 North Terrace, Adelaide, SA 5000
Ethics committee country [1] 309605 0
Australia
Date submitted for ethics approval [1] 309605 0
Approval date [1] 309605 0
04/09/2021
Ethics approval number [1] 309605 0
HREC/18/CALHN/659

Summary
Brief summary
Clinical Islet Transplantation at our center, akin to others internationally, achieves insulin independence rates of ~80% at 1 year in hypoglycemic unaware type 1 diabetics with poorly controlled disease. A major problem with current islet cell transplantation is the delivery of the islets into the portal circulation (via infusion into the liver). Up to 75% of the transplanted islet mass is lost within the first 24 hours due to low oxygen levels in the portal circulation and the instant blood mediated inflammatory reaction (IBMIR). Thus one of the major aims for the field of islet transplantation has been to develop a vascularised alternative site for islet transplantation that avoids the portal circulation.
The aim of this application is to change the current paradigm of beta cell replacement with intra-portal islet transplantation, by establishing a clinical protocol to place adult islets in a pre-vascularized “intracutaneous” space.
The intracutaneous space represents an attractive site for islet transplantation (ease of access, administration, monitoring, removal or replacement), however, it has been attempted unsuccessfully by groups in the past. The reason for failure of the ‘normal’ intracutaneous site is that the collagen structure produces a low oxygen (hypoxic) environment incapable of supporting islet survival and function. The BTM integrated into the intracutaneous site is much different! Implanting BTM into the intracutaneous site prior to islet transplant enables the formation of a dense vascular bed which is essential for islet survival and function.
It is hypothesised that the proposed pilot study will demonstrate that the techniques described result in the successful intracutaneous seeding of human islets capable of secreting insulin to control blood glucose levels.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114742 0
Prof Patrick Toby Hewlett Coates
Address 114742 0
Director of Kidney and Islet Transplantation,
Central Northern Adelaide Renal and Transplantation Service (CNARTS)
Royal Adelaide Hospital, Port Road, Adelaide 5000
South Australia, AUSTRALIA.
Country 114742 0
Australia
Phone 114742 0
+61 8 7074 2609
Fax 114742 0
Email 114742 0
[email protected]
Contact person for public queries
Name 114743 0
Prof Patrick Toby Hewlett Coates
Address 114743 0
Director of Kidney and Islet Transplantation,
Central Northern Adelaide Renal and Transplantation Service (CNARTS)
Royal Adelaide Hospital, Port Road, Adelaide 5000
South Australia, AUSTRALIA.
Country 114743 0
Australia
Phone 114743 0
+61 8 7074 2609
Fax 114743 0
Email 114743 0
[email protected]
Contact person for scientific queries
Name 114744 0
Prof Patrick Toby Hewlett Coates
Address 114744 0
Director of Kidney and Islet Transplantation,
Central Northern Adelaide Renal and Transplantation Service (CNARTS)
Royal Adelaide Hospital, Port Road, Adelaide 5000
South Australia, AUSTRALIA.
Country 114744 0
Australia
Phone 114744 0
+61 8 7074 2609
Fax 114744 0
Email 114744 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patient confidentiality


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.