Back to resultsWharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed With Type I Diabetes
Primary Purpose
Type1diabetes
Status
Active
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
ProTrans
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Type1diabetes focused on measuring type 1 diabetes, diabetes, MSC's, Mesenchymal, Stem Cells, Stromal, Wharton´s Jelly
Eligibility Criteria
Inclusion Criteria:
- A new written informed consent for participation of the study is required to be given before undergoing any study-specific procedures.
- Only patients that have previously been dosed by the IMP according to protocol Protrans-1 are eligible for a second dose of Protrans.
- No identified IMP related on-going adverse event, neither history of any adverse event that is evaluated potentially to be related to the previous IMP dosing in Protrans I.
- Clinical history compatible with type 1 diabetes diagnosed less than 3 years before enrolment. This also includes control patients not receiving IMP.
- Only male patients between 18-41 years of age will be included.
- Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.
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 infections unless treatment is not judged necessary by the investigators
- 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.
- 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).
Sites / Locations
- Karolinska Trial Alliance, Fas 1 enheten, Karolinska Universitetssjukhuset Huddinge
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Sham Comparator
Arm Label
Low dose
Medium dose
High dose
Control
Arm Description
3 patients receiving low dose
3 patients receiving medium dose
3 patients receiving high dose
6 patients
Outcomes
Primary Outcome Measures
The primary safety endpoint in this study is; safety parameters include adverse events, hypoglycemia and allergic reactions
To investigate the safety and tolerance after a repeated allogeneic infusion of Whartons Jelly Mesenchymal Stromal Cells (WJMSCs) intravenously in adult patients diagnosed with type 1 diabetes after one year following the repeated treatment.
Delta-change of C-peptide AreaUnder the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at day 372 following WJMSC infusion when compared to test performed before start of treatment.
To study changes in insulin requirements during one year following treatment .
Secondary Outcome Measures
Number of patients insulin independent (ADA criteria) at day 372.
To study changes in insulin requirements during one year following treatment .
Number of patients with daily insulin needs <0.25U/kg at day 372.
To study changes in insulin requirements during one year following treatment .
HbA1c at day 372
To study changes in HbA1c during one year following treatment.
Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) duration derived from the continuous glucose monitoring system® at day 372
To study changes in glucose levels during one year following treatment.
Delta change of levels of fasting C-peptide at day 372 when compared to test before start of treatment
To study changes in fasting C-peptide levels during one year following treatment.
Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372.
To study changes in C-peptide levels during one year following treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03973827
Brief Title
Wharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed With Type I Diabetes
Official Title
An Open Label, Parallel Single Center Trial of Wharton's Jelly Derived Allogeneic Mesenchymal Stromal Cells Repeatedly Treated to Preserve Endogenous Insulin Production in Adult Patients Diagnosed With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 17, 2019 (Actual)
Primary Completion Date
December 10, 2020 (Actual)
Study Completion Date
October 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NextCell Pharma Ab
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An open label, parallel single centre trial of Wharton's Jelly derived allogenic mesenchymal stromal cells repeated treatment to preserve endogenous insulin production in adult patients diagnosed with type 1 diabetes
Detailed Description
This is a phase (I)/II study, and the purpose of this study is to determine whether, in adult patients diagnosed for type 1 diabetes, a repeated allogeneic infusion of WJMSCs is safe and to study changes in beta-cell function, metabolic control and Diabetes Treatment Satisfaction. The study population will consist of 18 adult male patients, 18-41 years of age (inclusive at both ends) diagnosed (<3,5 years) with type 1 diabetes mellitus.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1diabetes
Keywords
type 1 diabetes, diabetes, MSC's, Mesenchymal, Stem Cells, Stromal, Wharton´s Jelly
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low dose
Arm Type
Experimental
Arm Description
3 patients receiving low dose
Arm Title
Medium dose
Arm Type
Experimental
Arm Description
3 patients receiving medium dose
Arm Title
High dose
Arm Type
Experimental
Arm Description
3 patients receiving high dose
Arm Title
Control
Arm Type
Sham Comparator
Arm Description
6 patients
Intervention Type
Drug
Intervention Name(s)
ProTrans
Other Intervention Name(s)
Allogeneic transplantation with WJMSCs
Intervention Description
Single infusion of 25, 100 or 200 million cells per patient.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo treatment
Intervention Description
Placebo Comparator: Sham transplantation (placebo) Single infusion with albumin and dmso in sodium chloride (identical concentrations as active treatment)
Primary Outcome Measure Information:
Title
The primary safety endpoint in this study is; safety parameters include adverse events, hypoglycemia and allergic reactions
Description
To investigate the safety and tolerance after a repeated allogeneic infusion of Whartons Jelly Mesenchymal Stromal Cells (WJMSCs) intravenously in adult patients diagnosed with type 1 diabetes after one year following the repeated treatment.
Time Frame
372 days
Title
Delta-change of C-peptide AreaUnder the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at day 372 following WJMSC infusion when compared to test performed before start of treatment.
Description
To study changes in insulin requirements during one year following treatment .
Time Frame
372 days
Secondary Outcome Measure Information:
Title
Number of patients insulin independent (ADA criteria) at day 372.
Description
To study changes in insulin requirements during one year following treatment .
Time Frame
372 days
Title
Number of patients with daily insulin needs <0.25U/kg at day 372.
Description
To study changes in insulin requirements during one year following treatment .
Time Frame
372 days
Title
HbA1c at day 372
Description
To study changes in HbA1c during one year following treatment.
Time Frame
372 days
Title
Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) duration derived from the continuous glucose monitoring system® at day 372
Description
To study changes in glucose levels during one year following treatment.
Time Frame
372 days
Title
Delta change of levels of fasting C-peptide at day 372 when compared to test before start of treatment
Description
To study changes in fasting C-peptide levels during one year following treatment.
Time Frame
372 days
Title
Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372.
Description
To study changes in C-peptide levels during one year following treatment.
Time Frame
372 days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
41 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A new written informed consent for participation of the study is required to be given before undergoing any study-specific procedures.
Only patients that have previously been dosed by the IMP according to protocol Protrans-1 are eligible for a second dose of Protrans.
No identified IMP related on-going adverse event, neither history of any adverse event that is evaluated potentially to be related to the previous IMP dosing in Protrans I.
Clinical history compatible with type 1 diabetes diagnosed less than 3 years before enrolment. This also includes control patients not receiving IMP.
Only male patients between 18-41 years of age will be included.
Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.
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.
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).- This criterion is only applicable to patients which receive study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Per-Ola Carlsson, PhD
Organizational Affiliation
Uppsala University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karolinska Trial Alliance, Fas 1 enheten, Karolinska Universitetssjukhuset Huddinge
City
Huddinge
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Wharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed With Type I Diabetes
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