Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression: A Safety Study
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|ClinicalTrials.gov Identifier: NCT00445913|
Recruitment Status : Completed
First Posted : March 9, 2007
Last Update Posted : February 15, 2016
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The proposed studies describe a randomized trial to evaluate the safety of a new diabetes-suppressive cell vaccine, consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40, CD80 and CD86 co-stimulatory molecules (immunoregulatory DC; iDC). The hypothesis to be tested in this study is that iDC are safe and without toxicity in established type 1 diabetic patients.
Fifteen (15) individuals exhibiting fully-established, insulin-dependent type 1 diabetics, without any diabetes-related complications, infectious disease, or other medical anomaly, will be enrolled to establish safety of the approach. 7/15 volunteers will be administered autologous control dendritic cells and 8/15 will be administered iDC. The study is anticipated to be complete by twelve (12) months.
Currently, other than a humanized anti-CD3 antibody with considerable side effects, there is no other means to reverse new-onset type 1 diabetes. These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to perhaps reverse it early on in the clinical process.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes||Biological: Diabetes-suppressive dendritic cell vaccine Biological: control dendritic cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression: A Safety Study|
|Study Start Date :||March 2007|
|Actual Primary Completion Date :||January 2012|
|Actual Study Completion Date :||February 2016|
Experimental: control dendritic cells
autologous dendritic cells that are not treated
Biological: control dendritic cells
The dendritic cells will be treated ex vivo with vehicle and cryopreserved in aliquots for subsequent intradermal administration into sites closest to the physical location of the pancreas inside the body. Physiologic, biologic and immunologic responses to these control dendritic cells will be evaluated over the period of the trial. The first group of volunteers will receive autologous dendritic cells without any ex vivo treatment (7/15) and the second group will be administered iDC (8/15). If there is no evidence of toxicity or adverse events associated with the dendritic cell vaccine, and only upon FDA and IRB approval we will initiate a new study comparing efficacy of control DC and iDC in improving glycemia and reversing autoimmunity in new-onset patients.
Experimental: AS ODN dendrtitic cells
autologous dendritic cells treated ex vivo with the mixture of the antisense oligonucleotides
Biological: Diabetes-suppressive dendritic cell vaccine
The dendritic cells will be treated ex vivo with the antisense oligonucleotides and cryopreserved in aliquots for subsequent intradermal administration into sites closest to the physical location of the pancreas inside the body. Physiologic, biologic and immunologic responses to the dendritic cell vaccine will be evaluated over the period of the trial. The first group of volunteers will receive autologous dendritic cells without any ex vivo treatment (7/15) and the second group will be administered iDC (8/15). If there is no evidence of toxicity or adverse events associated with the dendritic cell vaccine, and only upon FDA and IRB approval we will initiate a new study comparing efficacy of control DC and iDC in improving glycemia and reversing autoimmunity in new-onset patients.
Other Name: diabetes-suppressive dendritic cells
- The trial is designed to assure that the toxicity rate is acceptably low to warrant further study of the cell vaccine in efficacy trials. [ Time Frame: June 2011 ]
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|Ages Eligible for Study:||18 Years to 60 Years (Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
Patients with established type 1 diabetes mellitus who meet all inclusion criteria are eligible for enrollment in the study.
- All patients enrolled must be on insulin replacement therapy.
- Written informed consent conforming to the institutional guidelines obtained from the patient.
- Documented evidence of insulin-requiring type 1 diabetes of >5 years duration.
- Adequate immune competence, as indicated by positive reaction to one or more of the common DTH skin tests that are part of the Multitest CMITM test system (Pasteur-Merieux Connaught) and as indicated by the manufacturer. Also, proof of vaccination for tetanus (no more than 10 years must have elapsed between tetanus vaccination and the onset of this study).
- Age 18-35.
Adequate hematologic function:
- Absolute neutrophil count > 1,000/mm3
- Absolute lymphocyte count > 1,000/mm3
- Hemoglobin > 9 gm/dl
- Platelets > 100,000/mm3
Liver function tests:
- Bilirubin (total) < 1.7 mg/dl
- Alkaline phosphatase < 78 u/L (2 x ULN)
- SGOT < 54 u/L (2 x ULN)
- Lactic dehydrogenase < 180 u/L (2 x ULN)
- Sodium 135-145 mEq/L
- Potassium 3.5-5.0 mEq/L
- Bicarbonate 21-28 mEq/L
- Chloride 100-108 mmol/L
- Serum creatinine <4.5 mg/dL (3 x ULN)
- BUN 8-25 mg/dL
- No prior history of radiation therapy, immunotherapy, or chemotherapy
- Evidence of prior immunization to tetanus
- Absence of HIV, HSV, HBV, HCV viral infections
- At least four weeks since any prior radiation , immunotherapy or chemotherapy
- One or more of the Eligibility Criteria are not met.
- A significant history or current evidence of cardiac disease including, but not limited to, congestive heart failure, coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias; or myocardial infarction within the previous six months.
- Evidence of active infection requiring antibiotic therapy.
- History of other concurrent diseases.
- Pregnant or lactating women.
- Patients requiring systemic corticosteroids
- Any other immune disorder including but not limited to other autoimmune diseases like rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, or ankylosing spondylitis
- History of radiation therapy, immunotherapy, or chemotherapy
The following therapies cannot be administered while patients are undergoing treatment on this protocol:
- radiation therapy
- corticosteroids (except when administered in life-threatening circumstances) other particle or cell vaccine therapies
At the time of screening, the patients will be tested for evidence of the following viral infections: HIV, HBV, HCV, herpes, CMV and EBV. In addition, female volunteers will be asked to provide documentation from their physician stating that they have not tested positive for the HPV viral infection. Only patients testing negative for ALL these viral infections will be further considered. Should any volunteer be excluded on grounds of positivity for any of these infectious agents, they will be immediately notified and strongly advised to consult their physician. The data and the records will be maintained under lock and in the study participation file of the volunteer until the volunteer confirms in writing that they have notified their physician. At that time, these specific data may be submitted to the patient's physician ONLY DIRECTLY BY THE VOLUNTEER upon written request to the study principal investigator or immediately destroyed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00445913
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Massimo Trucco, M.D.||University of Pittsburgh|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||University of Pittsburgh|
|Other Study ID Numbers:||
NIDDK R33 DK683044 ( Other Identifier: NIH NIDDK )
|First Posted:||March 9, 2007 Key Record Dates|
|Last Update Posted:||February 15, 2016|
|Last Verified:||February 2016|
type 1 diabetes
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Immune System Diseases