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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00940173




Registration number
NCT00940173
Ethics application status
Date submitted
12/07/2009
Date registered
15/07/2009
Date last updated
20/10/2017

Titles & IDs
Public title
Open-label Investigation of the Safety and Effectiveness of DIABECELL(R) in Patients With Type I Diabetes Mellitus
Scientific title
A Phase I/IIa Open-label Investigation of the Safety and Effectiveness of DIABECELL(R) [Immunoprotected (Alginate-Encapsulated) Porcine Islets for Xenotransplantation] in Patients With Type I Diabetes Mellitus
Secondary ID [1] 0 0
LCT/DIA-06
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - DIABECELL(R)
Treatment: Devices - DIABECELL(R)
Treatment: Devices - DIABECELL(R)
Treatment: Devices - DIABECELL(R)

Other: Group 1 - Dose Group 1 (Receiving a dose of 10,000 IEQ/kg of DIABECELL(R))

Other: Group 2 - Dose Group 2 (Receiving a dose of 15,000 IEQ/kg of DIABECELL(R))

Other: Group 3 - Dose Group 3 (Receiving a dose of 20,000 IEQ/kg of DIABECELL(R))

Other: Group 4 - Dose Group 4 (Receiving a dose of 5,000 IEQ/kg of DIABECELL(R))


Treatment: Devices: DIABECELL(R)
10,000 IEQ/kg injected into the peritoneal cavity via laparoscopy

Treatment: Devices: DIABECELL(R)
15,000 IEQ/kg injected into the peritoneal cavity via laparoscopy

Treatment: Devices: DIABECELL(R)
20,000 IEQ/kg injected into the peritoneal cavity via laparoscopy

Treatment: Devices: DIABECELL(R)
5,000 IEQ/kg injected into the peritoneal cavity via laparoscopy
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To establish the safety of xenotransplantation of DIABECELL(R) [immunoprotected (alginate-encapsulated) porcine islets]
Timepoint [1] 0 0
52 Weeks
Primary outcome [2] 0 0
To establish preliminary evidence of the efficacy of DIABECELL(R), as measured by a reduction in serial HbA1C levels
Timepoint [2] 0 0
52 weeks
Secondary outcome [1] 0 0
To establish whether DIABECELL(R) causes an improvement in glucose lability determined from continuous glucose monitoring
Timepoint [1] 0 0
52 Weeks
Secondary outcome [2] 0 0
To determine whether DIABECELL(R) causes a reduction in hypoglycaemia and nocturnal hypoglycaemia
Timepoint [2] 0 0
52 Weeks
Secondary outcome [3] 0 0
To determine whether DIABECELL(R) causes a reduction in insulin dose
Timepoint [3] 0 0
52 Weeks
Secondary outcome [4] 0 0
To determine whether DIABECELL(R) causes an improvement in endogenous insulin secretion
Timepoint [4] 0 0
52 Weeks
Secondary outcome [5] 0 0
To determine whether DIABECELL(R) causes an improvement in quality-of-life
Timepoint [5] 0 0
52 Weeks

Eligibility
Key inclusion criteria
Inclusion criteria:

- Adults (males or females) in the age range 35 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 severe metabolic instability who cannot achieve acceptable
metabolic control without experiencing multiple episodes of severe hypoglycaemia,
often with unawareness; or

- with degrees of hypoglycaemia, who cannot be adequately managed with intensive insulin
therapy alone despite intensive diabetes management delivered by a qualified diabetes
team for at least six months prior to enrolment

- Patients should have an HbA1C =7% and =10% 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 0.5%.

- Plasma C-peptide <0.2 ng/ml following a glucagon stimulation test (Scheen et al. 1996)

- If female, no childbearing capability (those who are more than 2 years postmenopausal
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
Minimum age
35 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- 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 >10% during the 8-week baseline run-in period

- Body mass index (BMI) =30 kg/m2 or =20 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

- Previous history of peritoneal disease or abnormal findings at baseline laparoscopy

- Previous abdominal surgery, excluding uncomplicated appendectomy or cholecystectomy

- 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 >300 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:

1. 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

2. Previous cerebrovascular disease manifesting as transient ischaemic attacks
(TIAs) or stroke

3. Peripheral vascular disease with foot ulcer and/or previous amputation

4. History of New York Heart Association (NYHA) class II, III or IV congestive heart
failure (CHF) and/or chronic atrial fibrillation

5. 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

6. 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

7. Haematological disorders, including haemoglobin =110 g/L or platelet count <80 x
109/L

8. Peptic ulcer disease and/or history of previous gastrointestinal bleeding

9. Malignancy other than basal cell carcinoma

10. History of epilepsy

11. Untreated hypothyroidism

12. Known adrenal insufficiency

- History of drug, substance or alcohol abuse

- Current oestrogen (e.g. cortisol) therapy

- 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

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
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2013
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Diatranz Otsuka Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to establish the safety of xenotransplantation of
DIABECELL(R)[immunoprotected (alginate-encapsulated) porcine islets] in patients with
established type 1 diabetes mellitus, and to establish preliminary evidence of the efficacy
of DIABECELL(R), as measured by a reduction in serial hemoglobin A1c (HbA1C) levels.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00940173
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Baker, MB ChB
Address 0 0
Centre for Clinical Research and Effective Practice
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00940173