Clinical trial NCT00690066: PROCHYMAL® (Human Adult Stem Cells) for the Treatment of Recently Diagnosed Type 1 Diabetes Mellitus (T1DM)
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of PROCHYMAL® (Ex Vivo Cultured Adult Human Mesenchymal Stem Cells) for the Treatment of Recently Diagnosed Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Type 1 Diabetes
Diabetes Mellitus, Insulin-Dependent
Juvenile Diabetes
Keywords: T1DM
Type 1 Diabetes Mellitus
Type 1 Diabetes
Diabetes Mellitus, Insulin-Dependent
Juvenile Diabetes
Adult Human Stem Cells
Mesenchymal Stem Cells
MSCs
Insulin
Osiris
Prochymal
Lead sponsor: Mesoblast, Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2008-06-04
Enrollment: 63
Sex: ALL
Minimum age (years): 12
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish the safety and efficacy of multiple administrations of PROCHYMAL® in participants recently diagnosed with type 1 diabetes mellitus.

Detailed description: Diabetes mellitus refers to disorders in which the body has trouble controlling its blood glucose levels. There are two main types of diabetes: type 1 and type 2. Type 1 diabetes mellitus (T1DM), which is being studied in this trial, is an autoimmune disorder in which the body's own immune system attacks and destroys the cells that make insulin. These cells are called beta cells. As beta cells are destroyed, less insulin can be made. This causes blood sugar levels to increase above normal and can cause life-threatening hypo- and hyper-glycemic reactions. For this reason, people with type 1 diabetes must take insulin to help control their blood sugar levels. Over time, poorly controlled diabetes can lead to a variety of serious health conditions, including heart disease, stroke, blindness, amputations, kidney disease, and nerve damage. Insulin is the primary method of controlling diabetes by regulating blood glucose levels, but it may not reverse or prevent disease progression. The active ingredient in PROCHYMAL® is adult human mesenchymal stem cells (MSCs). MSCs have been shown to interact with the immune cells in the body, reducing inflammation and assisting in tissue repair. This study will help determine whether MSCs can protect normal pancreatic tissue from autoimmune attack and repair damaged pancreatic tissue, leading to an increase in insulin production and decrease in circulating blood glucose. The characteristics and biologic activity of PROCHYMAL®, along with a good safety profile in human trials to date, suggest that PROCHYMAL® may be a good candidate for addressing Type 1 Diabetes.

Eligibility criteria: Inclusion Criteria:

* Participant must have a diagnosis of type 1 diabetes mellitus based on the American Diabetes Association (ADA) criteria.
* Participant must be screened between 2 and 20 weeks from initial T1DM diagnosis
* Participants must be between the ages of 12 and 35 (inclusive).
* Participant must have at least one diabetes-related autoantibody present (either GAD or IA-2).
* Participant must have some beta cell function as determined by C-peptide testing (at least 0.2 pmol/mL (0.6 ng/mL) during MMTT.
* Participants must be willing to comply with "intensive diabetes management" as directed by the Investigator with the goal of maintaining blood glucose as close to normal as possible (i.e., glycosylated hemoglobin A1c (HbA1c) value of ≤ 7.0%).
* Participants must be willing to comply with the schedule of study visits and protocol requirements.

Exclusion Criteria:

* Participant has Body Mass Index (BMI) ≥ 30.
* Participant has evidence of retinopathy at baseline.
* Participant has abnormally high lipid levels.
* Participant has abnormal blood pressure.
* Participant has an abnormal serum creatinine.
* Participant has evidence of clinically significant proteinuria.
* Participant has diabetic ketoacidosis.
* Participant is being treated for a severe active infection of any type.
* A female participant who is breast-feeding, pregnant, or intends to become pregnant during the study.
* Participant with clinically relevant uncontrolled medical condition not associated with diabetes (e.g. hematologic, renal, hepatic, neurologic, cardiac, or respiratory).
* Participant has received an investigational drug (not approved by the FDA) for any indication 30 days prior to the screening visit.
* Participant is allergic to bovine or porcine products.
* Participant has evidence of active malignancy or prior history of active malignancy that has not been in remission for at least 5 years.
* Participant has any medical condition, which in the opinion of the Investigator, rendered his/her participation in this study unsuitable.

Primary outcomes:
measure: C-peptide area under the concentration curve (AUC) response (MMTT)
timeFrame: 1 year
Secondary outcomes:
measure: Peak C-peptide response (MMTT)
timeFrame: 2 years
measure: Basal C-peptide response
timeFrame: 2 years
measure: Total daily insulin dose (units/kg)
timeFrame: 2 years
measure: Glycosylated hemoglobin (HbA1c) levels
timeFrame: 2 years
measure: Number of severe and documented hypoglycemic events
timeFrame: 2 years
measure: Changes in levels of glutamic acid decarboxylase (GAD) or islet antigen 2 (IA-2) autoantibodies
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Division of Endocrinology & Metabolism
state: Alabama
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Institute
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Diabetes Research Institute
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Henderson
country: United States
facility: Desert Endocrinology CRC
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Alliance Against Diabetes
state: Nevada
city: Chapel Hill
country: United States
facility: University of North Carolina Diabetes Care Center
state: North Carolina
city: Charlotte
country: United States
facility: American Health Research, Inc.
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners - Center for Clinical Research
state: Ohio
city: Carlisle
country: United States
facility: Cumberland Valley Endocrinology
state: Pennsylvania
city: Bartlett
country: United States
facility: AM Diabetes & Endocrinology Center
state: Tennessee
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Optimum Clinical Research, Inc.
state: Utah
city: Norfolk
country: United States
facility: The Strelitz Diabetes Center, Eastern VA Medical School
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Health- West Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Clinical and Transitional Science Institute
state: Wisconsin
Study officials:
affiliation: Mesoblast, Inc.
name: Mahboob Rahman, MD
role: STUDY_DIRECTOR
References: