Wharton´s Jelly Derived Mesenchymal Stromal Cell Treatment of Adult Patients Diagnosed With Type I Diabetes

This is a combined phase I and phase II study, where the first part is an open, dose escalating study consisting of 9 male patients, 18-40 years of age. The second part is a randomized, double-blinded, placebo-controlled, phase I/II study in parallel design comparing allogeneic WJMSC treatment to placebo in adult patients diagnosed with type 1 diabetes. Besides safety, preservation of endogenous insulin production (measured as C-peptide concentrations) together with metabolic control, diabetes treatment satisfaction and immunological profile will be assessed.

A total number of 24 patients will be enrolled in the study and followed for one year after WJMSC/placebo treatment. Patients 18-40 years of age, both male and female, diagnosed for type 1 diabetes will be eligible. Providing informed consent and fulfillment of inclusion criteria and no exclusion criteria, they will within two years of diagnosis be randomized.

Inclusion criteria

• Written informed consent for participation of the study, given before undergoing any study-specific procedures
• Clinical history compatible with type 1 diabetes diagnosed less than 2 years before enrolment
• In the first part of the study patients 1-9 only male patients between 18-40 years of age will be included. In the second part of the study, patients 10-24, both male and female patients 18 to 40 years of age (inclusive at both ends) will be included.
• Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol
• Fasting plasma C-peptide concentration >0.12 nmol/L.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they are using effective methods of contraception during the study. Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly. Such methods include (in "Recommendations related to contraception and pregnancy testing in clinical trials", supplied from www.hma.eu/):

• Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation.

• oral
• intravaginal
• transdermal
• progestogen-only hormonal contracption associated with inhibition of ovulation

• oral
• injectable
• implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• total abstinence or vasectomized partner.

Exclusion criteria

• Inability to provide informed consent
• Patients with body mass index (BMI) > 30, or weight >100 kg
• Patients with weight <50 kg
• Patients with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris.
• Patients with uncontrolled hypertension (≥160/105 mmHg).
• Patients with active on-going infections.
• Patients with latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or has travelled in areas with high risk of tuberculosis or mycosis within the last 3 months.
• Patients with serological evidence of infection with HIV, Treponema pallidum, hepatitis B antigen (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.
• Patients with any immune suppressive treatment
• Patients with known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease-
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Patients with known, or previous, malignancy.
• Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin.
• Patients with GFR <80 ml/min/1.73 m2 body surface.
• Patients with proliferative retinopathy.
• Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with MSC.
• Known hypersensitivity against any excipients, i.e. dimethyl sulfoxide (DMSO).