Ignite Creation Date:
2024-05-06 @ 9:46 AM
Last Modification Date:
2024-10-26 @ 12:19 PM
Study NCT ID:
NCT03073577
Status:
RECRUITING
Last Update Posted:
2023-10-06
First Post:
2017-02-26
Brief Title:
Islet Transplantation Using PKX-001
Sponsor:
University of Alberta
Organization:
University of Alberta
Study Overview
Official Title:
Clinical Study Using Antiaging Glycopeptide PKX-001 in Islet Transplantation
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Islet Transplantation is a procedure used in people with difficult to control Type 1 Diabetes Insulin producing cells islets are isolated from a deceased donor pancreas After the cells are carefully isolated from the donor pancreas the islets are transplanted into the recipients liver These transplanted islets may produce insulin
One of the challenges with islet transplant is the death of some of the transplanted islets due to inflammation oxidative stress and exposure to diabetogenic immunosuppressive agents associated with islet functional impairment and graft loss especially linked to the use of calcineurin inhibitors including tacrolimus Tac
Antiaging glycopeptide PKX-001 is a small stable synthetic replica of antifreeze proteins AFPs which naturally occur in Arctic and Antarctic fish and have been shown protecting cells against harmful conditions PKX-001 is a new drug that has been shown in lab studies to help islet cells survive isolation and keep them healthy and functioning Most importantly animal studies have shown that islets treated with PKX-001 were protected from the immunosuppressant Tac toxicity and retained their function in animals receiving islet transplant
This study will involve up to 10 participants from the islet transplant waiting list at the Clinical Islet Transplant Program All participants will receive islets treated with the medication PKX-001 PKX-001 will be used only in the islet preservation process and will not be given to participants as medication
The purpose of this study is to confirm the safety of transplantation of PKX-001 treated islets and to evaluate the cytoprotective capacity of PKX-001 in islet transplantation especially its capacity to protect against Tac induced graft dysfunction
One of the challenges with islet transplant is the death of some of the transplanted islets due to inflammation oxidative stress and exposure to diabetogenic immunosuppressive agents associated with islet functional impairment and graft loss especially linked to the use of calcineurin inhibitors including tacrolimus Tac
Antiaging glycopeptide PKX-001 is a small stable synthetic replica of antifreeze proteins AFPs which naturally occur in Arctic and Antarctic fish and have been shown protecting cells against harmful conditions PKX-001 is a new drug that has been shown in lab studies to help islet cells survive isolation and keep them healthy and functioning Most importantly animal studies have shown that islets treated with PKX-001 were protected from the immunosuppressant Tac toxicity and retained their function in animals receiving islet transplant
This study will involve up to 10 participants from the islet transplant waiting list at the Clinical Islet Transplant Program All participants will receive islets treated with the medication PKX-001 PKX-001 will be used only in the islet preservation process and will not be given to participants as medication
The purpose of this study is to confirm the safety of transplantation of PKX-001 treated islets and to evaluate the cytoprotective capacity of PKX-001 in islet transplantation especially its capacity to protect against Tac induced graft dysfunction
Detailed Description:
Background
Clinical islet transplantation is today an accepted modality to treat selected diabetic patients with frequent hypoglycemic events and severe glycemic liability Although islet transplantation outcomes have improved significantly in highly specialized centers with a 5-year insulin independence rate exceeding 50 a proportion of patients require reintroduction of insulin later on Tac may be partly responsible for the limited islet durability and the need for multiple donors for each recipient in spite of its ability to prevent rejection and autoimmune recurrence In vitro studies of islets exposed to immunosuppressants have shown that Tac levels above 10-100 mgL cause vacuolization and destruction of islets in culture
Antifreeze proteins AFPs have generated considerable interest for their ability to protect cells under a variety of conditions However their large size restricts their use in medicine as they are unable to pass through capillaries into interstitial tissue and are unable to reach target cells
With these disadvantages of AFPs in mind Dr Geraldine-Castelot-Deliencourt Rouen France invented Antiaging glycopeptide which is later manufactured by ProtoKinetix Inc St Marys West Virginia US ProtoKinetix anti-aging glycopeptide PKX-001 is a small stable synthetic replica of the larger less stable AFP
PKX-001 has gone through a series of tests in various outsourced laboratories in Europe and North America These tests have proven its ability to protect a multitude of cell lines Hela cells adult fibroblast neonatal fibroblasts human neuronal stem cells mouse neuronal stem cells mouse islet cells blood platelets cluster of differentiation 34 CD34 cells and keratinocytes against ultraviolet A UVA ultraviolet C UVC Hydrogen Peroxide Inflammatory ILĪ² Time Temperature -196C -80C -3C 3C 4C 15C and 22C and Low Serum induced cell death at pHs from 53 -105 In addition to protecting cell survival PKX-001 also preserves cell functionality This has been tested via stem cell markers CD34 functionality tests and in vivo studies where PKX-001 treated transplanted islet cells were found to reduce blood glucose concentrations in diabetic mice by 40 by day 40 in comparison to islet cells which were transplanted into mice without first being exposed to PKX-001
In light of the beneficial roles of PKX-001 on cellular survival and functionality preservation our team have evaluated the cytoprotective capacity of PKX-001 in islet transplant especially its capacity of protection against the diabetogenic effect of Tac
In vitro assessment of human islets in culture with PKX-001 supplementation has also showed enhanced quality and yield of post-preservation human islets and protection against acute exposure to Tac at clinical relevant doses compared with those without PKX-001 supplementation Further analysis indicated that islets treated with PKX-001 had decreased oxidative stress improved insulin release by increasing islet exocytosis decreased islet loss during preservation due to apoptosis even in the presence of Tac
In vivo studies have complemented all in vitro findings above which demonstrated that PKX-001 supplementation suppressed early inflammation and improved islet engraftment with long-term efficacy
The proposed study is a phase I non-randomized open-label single arm prospective trial using retrospective controls
Ten adult Islet transplant candidates 18 years and older deemed appropriate for standard islet transplant at the University of Alberta Hospital will be enrolled in this investigation
Retrospective data from 10 islet transplant patients consented for chart review Protocol 000001120 entitled On-going review of islet transplant patients at the University of Alberta and Protocol 000001122 entitled Collaborative Islet Transplant Registry will be also collected
The standard of Care controls will be identified from the Islet Transplant program database period 2014 - 2016 and anonymized by a simple numbering system
Hypothesis
Transplantation of PKX-001 treated islets is safe and improves graft outcomes
Primary Objective
To demonstrate safety of transplantation of PKX-001 treated islets
Secondary Objectives
To assess efficacy of transplantation of PKX-001 treated islets To assess efficacy of addition of PKX-001 during islet preservation
Procedures
Prior to transplantation the patient is screened qualified listed for transplant and signs the informed consent form
At the time a suitable islet preparation becomes available the patient will receive allogeneic islet cells transplanted into patients intraportally by percutaneous transhepatic access
Islet transplant will be performed under the current immunosuppression regimen including induction AlemtuzumabBasiliximab and long-term immunosuppression PrografCellcept The engraftment regimen includes anti-inflammatory medications EtanerceptAnakinra and intravenous insulin and heparin The only additional intervention used in this pilot trial is the addition of the investigational agent PKX-001 to islet processing
Follow up
Participants will undergo a 3-month follow-up period following their initial or subsequent islet transplant
There are no study-specific follow-up visits required for this study Study subjects will be followed as per standard of care For the purpose of evaluating the primary and secondary endpoints the following measurements collected on study subjects at the time points indicated as per standard of care will be chart reviewed and recorded up to Day 30 post-transplant
Clinical Assessment by Transplant Fellow or Staff Post-Transplant Blood work as per Standard of Care Metabolic testing Ensure or Arginine Glucose Records for Self-Monitoring Incidence of Primary Non-Function see Glossary for definition Incidence of Adverse Events or Serious Adverse Events can be reported on any day post transplant Abdominal Ultrasound with Doppler report clinically significant findings The study will remain open to collect all 10 recipients follow-up data to 3 month post-transplant Primary and secondary outcome reporting will occur 90 days following the transplant of the last patient to the trial
Clinical islet transplantation is today an accepted modality to treat selected diabetic patients with frequent hypoglycemic events and severe glycemic liability Although islet transplantation outcomes have improved significantly in highly specialized centers with a 5-year insulin independence rate exceeding 50 a proportion of patients require reintroduction of insulin later on Tac may be partly responsible for the limited islet durability and the need for multiple donors for each recipient in spite of its ability to prevent rejection and autoimmune recurrence In vitro studies of islets exposed to immunosuppressants have shown that Tac levels above 10-100 mgL cause vacuolization and destruction of islets in culture
Antifreeze proteins AFPs have generated considerable interest for their ability to protect cells under a variety of conditions However their large size restricts their use in medicine as they are unable to pass through capillaries into interstitial tissue and are unable to reach target cells
With these disadvantages of AFPs in mind Dr Geraldine-Castelot-Deliencourt Rouen France invented Antiaging glycopeptide which is later manufactured by ProtoKinetix Inc St Marys West Virginia US ProtoKinetix anti-aging glycopeptide PKX-001 is a small stable synthetic replica of the larger less stable AFP
PKX-001 has gone through a series of tests in various outsourced laboratories in Europe and North America These tests have proven its ability to protect a multitude of cell lines Hela cells adult fibroblast neonatal fibroblasts human neuronal stem cells mouse neuronal stem cells mouse islet cells blood platelets cluster of differentiation 34 CD34 cells and keratinocytes against ultraviolet A UVA ultraviolet C UVC Hydrogen Peroxide Inflammatory ILĪ² Time Temperature -196C -80C -3C 3C 4C 15C and 22C and Low Serum induced cell death at pHs from 53 -105 In addition to protecting cell survival PKX-001 also preserves cell functionality This has been tested via stem cell markers CD34 functionality tests and in vivo studies where PKX-001 treated transplanted islet cells were found to reduce blood glucose concentrations in diabetic mice by 40 by day 40 in comparison to islet cells which were transplanted into mice without first being exposed to PKX-001
In light of the beneficial roles of PKX-001 on cellular survival and functionality preservation our team have evaluated the cytoprotective capacity of PKX-001 in islet transplant especially its capacity of protection against the diabetogenic effect of Tac
In vitro assessment of human islets in culture with PKX-001 supplementation has also showed enhanced quality and yield of post-preservation human islets and protection against acute exposure to Tac at clinical relevant doses compared with those without PKX-001 supplementation Further analysis indicated that islets treated with PKX-001 had decreased oxidative stress improved insulin release by increasing islet exocytosis decreased islet loss during preservation due to apoptosis even in the presence of Tac
In vivo studies have complemented all in vitro findings above which demonstrated that PKX-001 supplementation suppressed early inflammation and improved islet engraftment with long-term efficacy
The proposed study is a phase I non-randomized open-label single arm prospective trial using retrospective controls
Ten adult Islet transplant candidates 18 years and older deemed appropriate for standard islet transplant at the University of Alberta Hospital will be enrolled in this investigation
Retrospective data from 10 islet transplant patients consented for chart review Protocol 000001120 entitled On-going review of islet transplant patients at the University of Alberta and Protocol 000001122 entitled Collaborative Islet Transplant Registry will be also collected
The standard of Care controls will be identified from the Islet Transplant program database period 2014 - 2016 and anonymized by a simple numbering system
Hypothesis
Transplantation of PKX-001 treated islets is safe and improves graft outcomes
Primary Objective
To demonstrate safety of transplantation of PKX-001 treated islets
Secondary Objectives
To assess efficacy of transplantation of PKX-001 treated islets To assess efficacy of addition of PKX-001 during islet preservation
Procedures
Prior to transplantation the patient is screened qualified listed for transplant and signs the informed consent form
At the time a suitable islet preparation becomes available the patient will receive allogeneic islet cells transplanted into patients intraportally by percutaneous transhepatic access
Islet transplant will be performed under the current immunosuppression regimen including induction AlemtuzumabBasiliximab and long-term immunosuppression PrografCellcept The engraftment regimen includes anti-inflammatory medications EtanerceptAnakinra and intravenous insulin and heparin The only additional intervention used in this pilot trial is the addition of the investigational agent PKX-001 to islet processing
Follow up
Participants will undergo a 3-month follow-up period following their initial or subsequent islet transplant
There are no study-specific follow-up visits required for this study Study subjects will be followed as per standard of care For the purpose of evaluating the primary and secondary endpoints the following measurements collected on study subjects at the time points indicated as per standard of care will be chart reviewed and recorded up to Day 30 post-transplant
Clinical Assessment by Transplant Fellow or Staff Post-Transplant Blood work as per Standard of Care Metabolic testing Ensure or Arginine Glucose Records for Self-Monitoring Incidence of Primary Non-Function see Glossary for definition Incidence of Adverse Events or Serious Adverse Events can be reported on any day post transplant Abdominal Ultrasound with Doppler report clinically significant findings The study will remain open to collect all 10 recipients follow-up data to 3 month post-transplant Primary and secondary outcome reporting will occur 90 days following the transplant of the last patient to the trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None