Type 1 DiabetesPhase 1NCT02457858
Islet Isolation Using MnTE-2-PyP (BMX-010) - Pilot Study
A Phase 1 study testing Islet isolation using BMX-010 in people with Type 1 Diabetes, run by University of Alberta at 1 site in Canada.
Trial summary
In this study, the investigators hypothesize that the addition of antioxidant BMX-010 to perfusion solution, digestion solution and culture medium during islet isolation process, can lead to greater preservation of islet mass and metabolic function, such as improved islet yield, viability, and functional potency. Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Islet isolation using BMX-010
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2014to Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible the participant must have had type 1 diabetes mellitus (T1DM) for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:
- a. Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, a Clarke score ≥4, HYPO score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI >400/>300.
- b. Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
- Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
Who cannot join
- 1. History of enrollment in any other islet transplant trials (at the discretion of the investigator).
- 2. Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction <30%; or (c) evidence of ischemia on functional cardiac exam.
- 3. Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
- 4. Psychiatric disorder making the subject not a suitable candidate for transplantation, (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
- 5. History of non-adherence to prescribed regimens.
- 6. Active infection including Hepatitis C, Hepatitis B, HIV, or TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
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- 7. Any history of, or current malignancies except squamous or basal skin cancer.
- 8. BMI > 35 kg/m2 at screening visit.
- 9. Age less than 18 or greater than 68 years.
- 10. Measured glomerular filtration rate (GFR) <60 mL/min/1.73 m2.
- 11. Presence or history of macroalbuminuria (>300 mg/g creatinine).
- 12. Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
- 13. Baseline Hb < 105g/L (<10.5 g/dL) in women, or < 120 g/L (<12 g/dL) in men.
- 14. Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values >1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
- 15. Untreated proliferative retinopathy.
- 16. Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast-feeding.
- 17. Evidence of significant sensitization on PRA (at the discretion of the investigator).
- 18. Insulin requirement >1.0 U/kg/day
- 19. HbA1C >12%.
- 20. Uncontrolled hyperlipidemia [fasting LDL cholesterol > 3.4 mmol/L (133 mg/dL), treated or untreated; and/or fasting triglycerides > 2.3 mmol/L (90 mg/dL)].
- 21. Under treatment for a medical condition requiring chronic use of steroids.
- 22. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT/INR > 1.5.
- 23. Untreated Celiac disease.
- 24. Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Manganese Porphyrin MnTE-2-PyP (BMX - 010) Preservation of Islet Cell Mass and Function for Clinical Islet Transplantation
In this study, the investigators hypothesize that the addition of antioxidant BMX-010 to perfusion solution, digestion solution and culture medium during islet isolation process, can lead to greater preservation of islet mass and metabolic function, such as improved islet yield, viability, and functional potency.
This pilot study will involve up to 10 participants from the islet transplant waiting list at the Clinical Islet Transplant Program. All participants will receive islets isolated with the medication BMX-010. This is to assess the primary safety of BMX-010 on pancreata and islets. BMX-010 will be used only in the islet isolation process, and will not be given to participants as medication.
Read the detailed description
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 recipient's liver. These transplanted islets may produce insulin.
One of the challenges with islet transplant is the death of some of the islet cells during isolation and storage while awaiting transplant. This is caused, in part, by inflammation and "oxidization" of the islet tissue. Oxidization is a process that causes chemical stress on living cells. We are looking for medications that would reduce inflammation, reduce oxidization and minimize cell death during the isolation process.
BMX-010 is a new drug that we believe will help fight oxidization. It is an antioxidant that has been shown in lab studies to help islet cells survive isolation and keep them healthy and functioning. BMX-010 has not been used in human islet transplants in Canada before this study. BMX-010 has been used once in a patient who needed his pancreas removed - the islets were isolated and treated with BMX-010, then transplanted back into the patient (auto-islet transplant). These results are promising and there have been no significant side-effects reported. There have also been studies using human islets, treated with BMX-010, transplanted into mice.
In this study, 10 patients will receive islets treated with BMX-010. This is to assess the primary safety of BMX-010 on pancreata and islets. For pancreata and islets treated with BMX-010, BMX-010 will be added in the steps of pancreas perfusion, pancreas digestion and islet culturing. Participants in the study will receive their islet transplants under standard of care islet transplant for all aspects of peri- and post-transplant management including immunosuppression. Islet transplant patients are followed as part of their standard of care, therefore the data collected for this study will be measured as part of routine clinical care, requiring no extra study specific clinic visits. We will review data collected up to day 30 post-transplant and will include the following: patient and graft survival data, biochemical data from routine blood work, routine and for cause imaging, metabolic testing, initiation of interventions to treat complications, and reporting of any adverse or serious adverse events.
- Conditions
- Type 1 Diabetes
- Being tested
- Islet isolation using BMX-010
- Keywords
- Type 1 Diabetes, Islet Transplant
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Islet isolation using BMX-010Drug
Also called MnTE-2-PyP
BMX-010 will be used as a supplement in islet isolation process.
| Study group | Role | What they receive |
|---|---|---|
| BMX-010 treated islets | Experimental | Islet isolation using BMX-010 Receives: Drug: Islet isolation using BMX-010 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Islet yield using BMX-010, compared to current standard islet isolation data
To assess the safety of treating pancreata using BMX-010 prior to islet transplantation, treated islet isolation data will be measured and recorded, compared to current standard islet isolation data.
Measured: Day -1 pre-transplant (Islet yield will be recorded as standard-of-care routine practice)
Secondary outcomes (2)
Islet isolation quantity and quality using BMX-010, compared to current standard islet isolation data
To demonstrate efficacy of BMX-010 to improve islet isolation quantity and quality prior to islet transplantation, treated islet isolation data will be measured and recorded, compared to current standard islet isolation data.
Measured: Day -1 pre-transplant (Islet isolation quantity and quality will be recorded as standard-of-care routine practice)
AE/SAE morbidity within 1 month post-transplant
To demonstrate safety of BMX-010 in islet transplantation, Adverse Event/Serious Adverse Event morbidity within 1 month post-transplant will be recorded.
Measured: up to 1 month post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study startAug 2014
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- BioMimetix Pharmaceutical, Inc.
- Responsible party
- Sponsor
- Investigators
- James Shapiro, MD PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02457858
- Sponsor's protocol ID
- Pro00045961
- Status last verified
- Sep 2016
- First submitted
- 5 Aug 2014
- Last updated
- 11 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Manganese Porphyrin MnTE-2-PyP (BMX - 010) Preservation of Islet Cell Mass and Function for Clinical Islet Transplantation
- ClinicalTrials.gov ID
- NCT02457858
- Acronym / sponsor ID
- Pro00045961
- Conditions
- Type 1 Diabetes
- Keywords
- Type 1 Diabetes, Islet Transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- BioMimetix Pharmaceutical, Inc.
- Study start
- Aug 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 29 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the investigators hypothesize that the addition of antioxidant BMX-010 to perfusion solution, digestion solution and culture medium during islet isolation process, can lead to greater preservation of islet mass and metabolic function, such as improved islet yield, viability, and functional potency.
This pilot study will involve up to 10 participants from the islet transplant waiting list at the Clinical Islet Transplant Program. All participants will receive islets isolated with the medication BMX-010. This is to assess the primary safety of BMX-010 on pancreata and islets. BMX-010 will be used only in the islet isolation process, and will not be given to participants as medication.
Detailed description
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 recipient's liver. These transplanted islets may produce insulin.
One of the challenges with islet transplant is the death of some of the islet cells during isolation and storage while awaiting transplant. This is caused, in part, by inflammation and "oxidization" of the islet tissue. Oxidization is a process that causes chemical stress on living cells. We are looking for medications that would reduce inflammation, reduce oxidization and minimize cell death during the isolation process.
BMX-010 is a new drug that we believe will help fight oxidization. It is an antioxidant that has been shown in lab studies to help islet cells survive isolation and keep them healthy and functioning. BMX-010 has not been used in human islet transplants in Canada before this study. BMX-010 has been used once in a patient who needed his pancreas removed - the islets were isolated and treated with BMX-010, then transplanted back into the patient (auto-islet transplant). These results are promising and there have been no significant side-effects reported. There have also been studies using human islets, treated with BMX-010, transplanted into mice.
In this study, 10 patients will receive islets treated with BMX-010. This is to assess the primary safety of BMX-010 on pancreata and islets. For pancreata and islets treated with BMX-010, BMX-010 will be added in the steps of pancreas perfusion, pancreas digestion and islet culturing. Participants in the study will receive their islet transplants under standard of care islet transplant for all aspects of peri- and post-transplant management including immunosuppression. Islet transplant patients are followed as part of their standard of care, therefore the data collected for this study will be measured as part of routine clinical care, requiring no extra study specific clinic visits. We will review data collected up to day 30 post-transplant and will include the following: patient and graft survival data, biochemical data from routine blood work, routine and for cause imaging, metabolic testing, initiation of interventions to treat complications, and reporting of any adverse or serious adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BMX-010 treated islets | Experimental | Drug: Islet isolation using BMX-010Islet isolation using BMX-010 |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- To be eligible the participant must have had type 1 diabetes mellitus (T1DM) for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:
- a. Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, a Clarke score ≥4, HYPO score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI >400/>300.
- b. Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
- Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
Key exclusion criteria (24 listed)
- 1. History of enrollment in any other islet transplant trials (at the discretion of the investigator).
- 2. Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction <30%; or (c) evidence of ischemia on functional cardiac exam.
- 3. Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
- 4. Psychiatric disorder making the subject not a suitable candidate for transplantation, (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
- 5. History of non-adherence to prescribed regimens.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Islet isolation using BMX-010Also: MnTE-2-PyPBMX-010 will be used as a supplement in islet isolation process. | Drug | BMX-010 treated islets |
Primary outcome
Islet yield using BMX-010, compared to current standard islet isolation data
Time frame: Day -1 pre-transplant (Islet yield will be recorded as standard-of-care routine practice)
To assess the safety of treating pancreata using BMX-010 prior to islet transplantation, treated islet isolation data will be measured and recorded, compared to current standard islet isolation data.
2 secondary outcomes
Islet isolation quantity and quality using BMX-010, compared to current standard islet isolation data
Time frame: Day -1 pre-transplant (Islet isolation quantity and quality will be recorded as standard-of-care routine practice)
AE/SAE morbidity within 1 month post-transplant
Time frame: up to 1 month post-transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
- Clinical Islet Transplant Program at University of AlbertaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Shapiro, MD PhD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Islet isolation using BMX-010 in people with Type 1 Diabetes, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Islet yield using BMX-010, compared to current standard islet isolation data (time frame: Day -1 pre-transplant (Islet yield will be recorded as standard-of-care routine practice)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2022.