Type 1 Diabetes MellitusNCT00678990
Heparinized Islets in Clinical Islet Transplantation
A study testing Transplantation of islets with heparin coating in people with Type 1 Diabetes Mellitus, run by Corline Biomedical AB at 2 sites in Sweden.
Trial summary
In this study the islets will be surface modified to carry immobilised heparin (Corline Heparin Conjugate) prior to transplantation. The primary objective is to investigate safety and efficacy of allogeneic islet transplantation using islets coated with immobilised heparin. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Transplantation of islets with heparin coating
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesSweden
- Study dates
- Jan 2019to Dec 2019
- Phase
- Interventional
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients age 18 to 65 years of age.
- Ability to understand and provide written informed consent.
- Mentally stable and able to comply with the procedures of the study protocol.
- Clinical history compatible with type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years at the time of enrolment.
- Stimulated C-peptide < 0.3 ng/mL (0.1 nmol/L) in response to a MMTT, before first islet transplantation.
- All subjects must have received medical treatment of their diabetes under the guidance from an experienced endocrinologist.
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- If not previously transplanted the patient must also have;
- At least one episode of severe hypoglycaemia in the past 1 year defined as an event with at least one of the following symptoms; memory loss, confusion, uncontrollable behaviour, unusual difficulty in awakening, suspected seizure, loss of consciousness, or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood/plasma glucose level < 54 mg/dl (3.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration OR
- Reduced awareness of hypoglycaemia as defined by a Clarke score of 4 or more.
Who cannot join
- Patients who meet any of these criteria are not eligible for participation in the study:
- Patients with prior organ transplants other than a kidney graft and/or islets.
- Patients with body mass index (BMI) > 30.
- Insulin requirement > 1 Unit/kg/day at screening.
- Consistently abnormal liver function tests (> 1.5 x ULN on two consecutive measurements > 2 weeks apart), at screening.
- Proliferative untreated diabetic retinopathy
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- Increased risk for thrombosis (ex. homozygous APC-resistance) or bleeding (INR>1.5)
- Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
- Patients with increased cardiac risk defined as;
- unstable coronary artery disease requiring hospitalization or revascularization within 6 months prior to baseline visit
- chronic heart failure which required hospitalization 30 days prior to baseline visit
- Patients with active infections, unless treatment is not judged necessary by the investigators
- Patients with serological evidence of infection with HIV, hepatitis B (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.
- Patients with active peptic ulcer disease, symptomatic gallstones or portal hypertension.
- Patients who are pregnant or breastfeeding, or who intend to become pregnant.
- Sexually active females who are not:
- post-menopausal,
- surgically sterile, or
- using a highly effective method of contraception, such as: intra uterine device, oral contraceptives, implants, injectables or barrier devices combined with spermicidal gel
- Active alcohol or substance abuse
- Patients with evidence of high-level sensitization (PRA> 50% with flow cytometry).
- Patients with psychological conditions that make it unsafe to undergo islet transplantation or which preclude compliance with prescribed therapy
- HbA1c >11% (International standard) corresponding to IFCC calibration 97 mmol/mol, at screening.
- Medical history of egg allergy
- Patients with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplant
- Patients participating in or having participated in any other clinical drug studies in the past four weeks.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Department of Transplantation Surgery, Karolinska University Hospital
Stockholm, SE-141 86
Torbjörn Lundgren, MD, +46 73 6994946, torbjorn.lundgren@karolinska.se
Torbjörn Lundgren, MD
Department of Transplantation and Liver Surgery, Uppsala University Hospital
Uppsala, SE-751 85
Tomas Lorant, MD, +46 18 6110000, tomas.lorant@surgsci.uu.se
Tomas Lorant, MD
About this study
Official title: Open Study to Evaluate Safety and Efficacy of Allogenic Islet Transplantation Using Islets Coated With Immobilised Heparin
In this study the islets will be surface modified to carry immobilised heparin (Corline Heparin Conjugate) prior to transplantation. The primary objective is to investigate safety and efficacy of allogeneic islet transplantation using islets coated with immobilised heparin. The modification with heparin has been shown to protect the islets from being attacked by the immediate defence systems in blood (coagulation and inflammation), so that a larger portion of the islets will survive the initial phase and engraft. Evaluation will be based on metabolic and blood chemistry parameters.
Read the detailed description
Transplantation of islets of Langerhans isolated from donated organs is a promising therapy for diabetes type 1. The results so far have, however, not met with the expectations due to relatively low efficiency. Even in situations where the patients have become insulin-free, it has been estimated that the transplanted islet mass is less than 25% of the islet mass of a healthy individual, which in many cases has required repeated use of insulin injections. The islets are transferred to the patient by an infusion drop to the liver via the portal vein.
Researches within the Nordic Network for Clinical Islet Transplantation have in a series of publications shown that the islets are subject to a violent immunological reaction that is non-specific with regard to the individual patient (IBMIR) during the initial contact with blood (Moberg et al, Lancet 2002, among several). The IBMIR reaction is in the earliest phase mediated by coagulation and complement reactions.
In this study the islets will be surface modified to carry immobilised heparin (Corline Heparin Conjugate) prior to transplantation. The primary objective is to protect the islets from being attacked by IBMIR so that a larger portion of the islets will survive the initial phase and engraft. In a paper published by the research group (Cabric et. al., Diabetes, May 2007), the beneficial effects of immobilised heparin on the islets to counteract IBMIR were shown by experiments at the lab bench and in experimental animals.
The evaluation of the transplantations in this study will be based on metabolic and blood chemistry parameters, similar to the evaluations of other transplanted patients within the Nordic Network.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Transplantation of islets with heparin coating
- Keywords
- Islets of Langerhans, islets, heparin
- 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.
Transplantation of islets with heparin coatingProcedure or surgery
Transplantation of islets with heparin coating
| Study group | Role | What they receive |
|---|---|---|
| Open, single arm | Experimental | Transplantation of islets with heparin coating. Receives: Procedure: Transplantation of islets with heparin coating |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Number of and grade of Serious Adverse events during the first 105 days after transplantation and Adverse events during the first 75 days after transplantation.
Measured: 105 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2008 (estimated)
- Study startJan 2019 (estimated)
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Diabetes MellitusStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Corline Biomedical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tomas Lorant, Principal investigator, Uppsala University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00678990
- Sponsor's protocol ID
- SAL-01
- Status last verified
- Dec 2018
- First submitted
- 14 May 2008
- Last updated
- 10 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Study to Evaluate Safety and Efficacy of Allogenic Islet Transplantation Using Islets Coated With Immobilised Heparin
- ClinicalTrials.gov ID
- NCT00678990
- Acronym / sponsor ID
- SAL-01
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Islets of Langerhans, islets, heparin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Corline Biomedical ABIndustry (pharma, biotech, devices)
- Study start
- Jan 2019 (estimated)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 16 May 2008 (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 islets will be surface modified to carry immobilised heparin (Corline Heparin Conjugate) prior to transplantation. The primary objective is to investigate safety and efficacy of allogeneic islet transplantation using islets coated with immobilised heparin. The modification with heparin has been shown to protect the islets from being attacked by the immediate defence systems in blood (coagulation and inflammation), so that a larger portion of the islets will survive the initial phase and engraft. Evaluation will be based on metabolic and blood chemistry parameters.
Detailed description
Transplantation of islets of Langerhans isolated from donated organs is a promising therapy for diabetes type 1. The results so far have, however, not met with the expectations due to relatively low efficiency. Even in situations where the patients have become insulin-free, it has been estimated that the transplanted islet mass is less than 25% of the islet mass of a healthy individual, which in many cases has required repeated use of insulin injections. The islets are transferred to the patient by an infusion drop to the liver via the portal vein.
Researches within the Nordic Network for Clinical Islet Transplantation have in a series of publications shown that the islets are subject to a violent immunological reaction that is non-specific with regard to the individual patient (IBMIR) during the initial contact with blood (Moberg et al, Lancet 2002, among several). The IBMIR reaction is in the earliest phase mediated by coagulation and complement reactions.
In this study the islets will be surface modified to carry immobilised heparin (Corline Heparin Conjugate) prior to transplantation. The primary objective is to protect the islets from being attacked by IBMIR so that a larger portion of the islets will survive the initial phase and engraft. In a paper published by the research group (Cabric et. al., Diabetes, May 2007), the beneficial effects of immobilised heparin on the islets to counteract IBMIR were shown by experiments at the lab bench and in experimental animals.
The evaluation of the transplantations in this study will be based on metabolic and blood chemistry parameters, similar to the evaluations of other transplanted patients within the Nordic Network.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open, single arm | Experimental | Procedure: Transplantation of islets with heparin coatingTransplantation of islets with heparin coating. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female patients age 18 to 65 years of age.
- Ability to understand and provide written informed consent.
- Mentally stable and able to comply with the procedures of the study protocol.
- Clinical history compatible with type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years at the time of enrolment.
- Stimulated C-peptide < 0.3 ng/mL (0.1 nmol/L) in response to a MMTT, before first islet transplantation.
Key exclusion criteria (26 listed)
- Patients with prior organ transplants other than a kidney graft and/or islets.
- Patients with body mass index (BMI) > 30.
- Insulin requirement > 1 Unit/kg/day at screening.
- Consistently abnormal liver function tests (> 1.5 x ULN on two consecutive measurements > 2 weeks apart), at screening.
- Proliferative untreated diabetic retinopathy
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 |
|---|---|---|
| Transplantation of islets with heparin coatingTransplantation of islets with heparin coating | Procedure or surgery | Open, single arm |
Primary outcome
Safety
Time frame: 105 days
Number of and grade of Serious Adverse events during the first 105 days after transplantation and Adverse events during the first 75 days after transplantation.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2018.
- Individual participant dataSharing planned: No
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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.
Tomas Lorant principal investigator
Uppsala University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transplantation of islets with heparin coating in people with Type 1 Diabetes Mellitus, run by Corline Biomedical AB at 2 sites in Sweden.
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 9 inclusion and 26 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: status not confirmed, as of the sponsor's last update on 10 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tomas Lorant (+46 18 6110000, tomas.lorant@surgsci.uu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: 105 days). 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 10 Dec 2018.