Type 1 DiabetesPhase 1/2NCT01739829
Open-label Investigation of the Safety and Effectiveness of DIABECELL® in Patients With Type 1 Diabetes Mellitus
A Phase 1/2 study testing DIABECELL (R) in people with Type 1 Diabetes, run by Diatranz Otsuka Limited at 1 site in Argentina.
Trial summary
The purpose of this study is to establish the safety and efficacy of xenotransplantation of DIABECELL® in patients with established type 1 diabetes mellitus Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- DIABECELL (R)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteArgentina
- Study dates
- Aug 2011to Jun 2014
- Phase
- Phase 1/2
- 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
- Adults (males or females) in the age range 18 to 65 years
- Diagnosis of type 1 diabetes mellitus (minimum duration of 5 years) in accordance with the American Diabetes Association's criteria. Patients should have been treated continuously with insulin since diagnosis (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2002)
- Patients with established brittle type I diabetes mellitus with a well-documented chronic history of metabolic instability who cannot achieve acceptable metabolic control (which may include treatment with the use of a continuous insulin infusion pump) without experiencing multiple episodes of hypoglycaemia, often with unawareness
- Patients should have an HbA1C ≥7% and ≤15% calculated as the average of the last four consecutive HbA1C readings during the 8-week baseline run-in period. The difference between the highest and lowest of the four HbA1C reading should be no more than 1.0%.
- Plasma C-peptide <0.3 ng/ml following a glucagon stimulation test (Scheen et al. 1996)
- If female, no childbearing capability (those who are more than two years post menopausal or have undergone voluntary sterilisation can be considered for enrolment)
- Provision of written informed consent. Patients will be required to agree to comply with all tests and visits specified in the protocol, and they (and their partners/close contacts) will also be required to consent to long-term microbiological monitoring, which is an integral part of the study
Who cannot join
- Type 2 diabetes, defined as age of onset >30 years and/or a history of treatment with oral hypoglycaemic medications and/or insulin resistance (defined as an insulin dose requirement ≥1.2 U/kg/day)
- An average HbA1C < 7% and >15% during the 8-week baseline run-in period
- Body mass index (BMI) ≥30 kg/m2 or ≤9 kg/m2
- Active infection, with plasma C-reactive protein ≥10 mg/L at baseline
- Previous receipt of an organ, skin graft, or other tissue transplant from a human or animal donor
- Treatment with immunosuppressive medications for another medical condition
Show all 31Show fewer
- Previous history of peritoneal disease or abnormal findings at baseline laparoscopy
- Previous abdominal surgery, excluding uncomplicated appendectomy, cholecystectomy or caesarean section
- History of pelvic inflammatory disease or endometriosis
- Inability to tolerate oral medications or a history of significant malabsorption
- HIV antibody and/or risk factors for HIV infection
- Positive hepatitis C antibody, positive hepatitis B surface antigen and hepatitis B core antibody
- Kidney disease, defined as serum creatinine >130 μmol/L in men and >110 μmol/L in women and/or urinary albumin >500 mg/L and/or haematuria and/or active urinary sediment or casts
- Diabetes microvascular complications defined as untreated, potentially vision-threatening proliferative or pre-proliferative retinopathy or maculopathy; painful peripheral neuropathy; autonomic neuropathy manifesting as postural hypotension; gastroparesis or diabetic enteropathy
- Diagnosis of coeliac disease and history of gastrointestinal symptoms including chronic or recurrent diarrhoea, malabsorption, weight loss and abdominal distension or bloating on exposure to gluten products in the diet
- Serious comorbid conditions that are likely to affect participation in the study, including:
- Previous coronary heart disease manifesting as non-ST elevation myocardial infarction (NSTEMI), Q-wave infarction or unstable angina; coronary artery bypass graft (CABG); or percutaneous angioplasty
- Previous cerebrovascular disease manifesting as transient ischaemic attacks (TIAs) or stroke
- Peripheral vascular disease with previous amputation
- History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation
- Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalisation for decompensation; a requirement for mechanical ventilation at any stage; or long-term treatment with oral corticosteroids
- Liver disease with abnormal liver function tests defined as serum bilirubin ≥20 µmol/L, and/or ALT ≥100 U/L, and/or GGT ≥100 U/L, and/or albumin <35 g/L
- Haematological disorders, including haemoglobin ≤110 g/L or platelet count <80 x 109/L
- Peptic ulcer disease and/or history of previous gastrointestinal bleeding
- Malignancy other than basal cell carcinoma
- History of epilepsy
- Untreated hypothyroidism
- Known adrenal insufficiency
- History of drug, substance or alcohol addiction
- Any factor detected from psychometric evaluation at Visit 2 Pre-Tx during the screening period which may in the opinion of the Clinical Psychologist affect an individual's ability to fully participate in the study
- Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, mental illness, or a history of non-adherence to appointments or treatments
Trial locations and contacts
1 site in 1 country.
Argentina1 site
Hospital Interzonal General de Agudos Eva Perón
Buenos Aires
About this study
Official title: A Phase I/IIa Open-label Investigation of the Safety and Effectiveness of DIABECELL® [Immunoprotected (Alginate-Encapsulated) Porcine Islets for Xenotransplantation] in Patients With Type 1 Diabetes Mellitus
The purpose of this study is to establish the safety and efficacy of xenotransplantation of DIABECELL® in patients with established type 1 diabetes mellitus
Read the detailed description
Intraperitoneal islet transplantation has the potential to ameliorate type 1 diabetes mellitus and avert the long-term consequences of chronic diabetes which cannot be achieved by conventional insulin treatment.
As donor human islets are not available in sufficient numbers, porcine islets are the best alternative source as they are recognised as the most physiologically compatible xenogeneic insulin-producing cells. Although the use of pig-derived cells raises the risk of xenotic infections, this can be minimised by obtaining cells from designated pathogen-free (DPF) animals bred in isolation and monitored to be free of specified pathogens. The worldwide experience to date in more than 200 patients who have received transplants of pig tissue has not demonstrated evidence of transmitted xenotic infections.
As animal-derived tissues have to be protected from immune rejection when transplanted into humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine islets are preferably transplanted without the use of immunosuppressive drugs which cause significant morbidity. To protect them from immune rejection, the islets can be encapsulated in alginate microcapsules which permit the inward passage of nutrients and glucose and the outward passage of insulin. Alginate-encapsulated porcine islets transplanted without immunosuppressive drugs have survived rejection for many months in animal studies, and have been retrieved from a diabetic patient over 9.5 years after intraperitoneal transplantation and shown to contain viable islets that stain positive for insulin.
DIABECELL® comprises neonatal porcine islets encapsulated in alginate microcapsules. DIABECELL® has been safely transplanted in healthy and diabetic mice, rats, rabbits, dogs and non-human primates. Following DIABECELL® transplants, the requirement for daily insulin was significantly reduced in diabetic rats and non-human primates.
The optimal dose and frequency of transplantation of the current DIABECELL® preparation for the treatment of type 1 diabetes in humans can only be determined in clinical trials. The intention of this phase I/IIa clinical trial is to obtain at least 52 weeks safety and preliminary efficacy data in type 1 diabetic patients following transplantation of two low effective doses of DIABECELL® into the peritoneal cavity.
- Conditions
- Type 1 Diabetes
- Being tested
- DIABECELL (R)
- Keywords
- xenotransplantation, type 1 diabetes, porcine islets
- 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.
DIABECELL (R)Device
10,000 IEQ per kg body weight (Total Dose) Administered in two doses: 5,000 IEQ/kg three months apart.
DIABECELL (R)Device
20,000 IEQ per kg body weight (Total Dose) Administered in two doses: 10,000 IEQ/kg three months apart
| Study group | Role | What they receive |
|---|---|---|
| DIABECELL group 1 | Experimental | 10,000 IEQ per kg body weight (Total Dose) Administered in two doses: 5,000 IEQ/kg three months apart. Receives: Device: DIABECELL (R) |
| DIABECELL group 2 | Experimental | 20,000 IEQ per kg body weight (Total Dose) Administered in two doses: 10,000 IEQ/kg three months apart Receives: Device: DIABECELL (R) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the safety and efficacy of xenotransplantation of DIABECELL
- safety determined by occurence of hypoglycaemic events, occurence of perioperative reactions, occurence of adverse/serious adverse events, monitoring laboratory test results (including xenogeneic infection status), conducting physical examination, ECG
- efficacy determined by change in HbA1c,daily insulin dose, transplant estimate function score, time spent in euglycaemia, occurence of hypoglycaemic events, quality of life assessment
- the primary endpoint will be a reduction in the unaware hypoglycaemic event rate combined with no increase in HbA1c
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2012 (estimated)
- Study startAug 2011
- Primary completionJun 2014
- Study completionJun 2014
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diatranz Otsuka Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adrián Abalovich, Principal investigator, Eva Perón Hospital, San Martín
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01739829
- Sponsor's protocol ID
- LCT/DIA-09
- Status last verified
- Oct 2017
- First submitted
- 26 Nov 2012
- Last updated
- 20 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Open-label Investigation of the Safety and Effectiveness of DIABECELL® [Immunoprotected (Alginate-Encapsulated) Porcine Islets for Xenotransplantation] in Patients With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01739829
- Acronym / sponsor ID
- LCT/DIA-09
- Conditions
- Type 1 Diabetes
- Keywords
- xenotransplantation, type 1 diabetes, porcine islets
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Diatranz Otsuka LimitedIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 4 Dec 2012 (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.
The purpose of this study is to establish the safety and efficacy of xenotransplantation of DIABECELL® in patients with established type 1 diabetes mellitus
Detailed description
Intraperitoneal islet transplantation has the potential to ameliorate type 1 diabetes mellitus and avert the long-term consequences of chronic diabetes which cannot be achieved by conventional insulin treatment.
As donor human islets are not available in sufficient numbers, porcine islets are the best alternative source as they are recognised as the most physiologically compatible xenogeneic insulin-producing cells. Although the use of pig-derived cells raises the risk of xenotic infections, this can be minimised by obtaining cells from designated pathogen-free (DPF) animals bred in isolation and monitored to be free of specified pathogens. The worldwide experience to date in more than 200 patients who have received transplants of pig tissue has not demonstrated evidence of transmitted xenotic infections.
As animal-derived tissues have to be protected from immune rejection when transplanted into humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine islets are preferably transplanted without the use of immunosuppressive drugs which cause significant morbidity. To protect them from immune rejection, the islets can be encapsulated in alginate microcapsules which permit the inward passage of nutrients and glucose and the outward passage of insulin. Alginate-encapsulated porcine islets transplanted without immunosuppressive drugs have survived rejection for many months in animal studies, and have been retrieved from a diabetic patient over 9.5 years after intraperitoneal transplantation and shown to contain viable islets that stain positive for insulin.
DIABECELL® comprises neonatal porcine islets encapsulated in alginate microcapsules. DIABECELL® has been safely transplanted in healthy and diabetic mice, rats, rabbits, dogs and non-human primates. Following DIABECELL® transplants, the requirement for daily insulin was significantly reduced in diabetic rats and non-human primates.
The optimal dose and frequency of transplantation of the current DIABECELL® preparation for the treatment of type 1 diabetes in humans can only be determined in clinical trials. The intention of this phase I/IIa clinical trial is to obtain at least 52 weeks safety and preliminary efficacy data in type 1 diabetic patients following transplantation of two low effective doses of DIABECELL® into the peritoneal cavity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DIABECELL group 1 | Experimental | Device: DIABECELL (R)10,000 IEQ per kg body weight (Total Dose) Administered in two doses: 5,000 IEQ/kg three months apart. |
| DIABECELL group 2 | Experimental | Device: DIABECELL (R)20,000 IEQ per kg body weight (Total Dose) Administered in two doses: 10,000 IEQ/kg three months apart |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults (males or females) in the age range 18 to 65 years
- Diagnosis of type 1 diabetes mellitus (minimum duration of 5 years) in accordance with the American Diabetes Association's criteria. Patients should have been treated continuously with insulin since diagnosis (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2002)
- Patients with established brittle type I diabetes mellitus with a well-documented chronic history of metabolic instability who cannot achieve acceptable metabolic control (which may include treatment with the use of a continuous insulin infusion pump) without experiencing multiple episodes of hypoglycaemia, often with unawareness
- Patients should have an HbA1C ≥7% and ≤15% calculated as the average of the last four consecutive HbA1C readings during the 8-week baseline run-in period. The difference between the highest and lowest of the four HbA1C reading should be no more than 1.0%.
- Plasma C-peptide <0.3 ng/ml following a glucagon stimulation test (Scheen et al. 1996)
Key exclusion criteria (31 listed)
- Type 2 diabetes, defined as age of onset >30 years and/or a history of treatment with oral hypoglycaemic medications and/or insulin resistance (defined as an insulin dose requirement ≥1.2 U/kg/day)
- An average HbA1C < 7% and >15% during the 8-week baseline run-in period
- Body mass index (BMI) ≥30 kg/m2 or ≤9 kg/m2
- Active infection, with plasma C-reactive protein ≥10 mg/L at baseline
- Previous receipt of an organ, skin graft, or other tissue transplant from a human or animal donor
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 |
|---|---|---|
| DIABECELL (R)10,000 IEQ per kg body weight (Total Dose) Administered in two doses: 5,000 IEQ/kg three months apart. | Device | DIABECELL group 1 |
| DIABECELL (R)20,000 IEQ per kg body weight (Total Dose) Administered in two doses: 10,000 IEQ/kg three months apart | Device | DIABECELL group 2 |
Primary outcome
To establish the safety and efficacy of xenotransplantation of DIABECELL
Time frame: 2 years
* safety determined by occurence of hypoglycaemic events, occurence of perioperative reactions, occurence of adverse/serious adverse events, monitoring laboratory test results (including xenogeneic infection status), conducting physical examination, ECG * efficacy determined by change in HbA1c,daily insulin dose, transplant estimate function score, time spent in euglycaemia, occurence of hypoglycaemic events, quality of life assessment * the primary endpoint will be a reduction in the unaware hypoglycaemic event rate combined with no increase in HbA1c
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 20 Oct 2017.
- Diatranz Otsuka LimitedLink 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.
Adrián Abalovich principal investigator
Eva Perón Hospital, San Martín
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DIABECELL (R) in people with Type 1 Diabetes, run by Diatranz Otsuka Limited at 1 site in Argentina.
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 7 inclusion and 31 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 20 Oct 2017. 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 Argentina. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To establish the safety and efficacy of xenotransplantation of DIABECELL (time frame: 2 years). 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 20 Oct 2017.