NCT00445913

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2007

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2007

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

March 7, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 9, 2007

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
4.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

February 15, 2016

Status Verified

February 1, 2016

Enrollment Period

4.8 years

First QC Date

March 7, 2007

Last Update Submit

February 12, 2016

Conditions

Type 1 Diabetes

Keywords

type 1 diabetesdendritic cellscell vaccinesafetyreversal

Outcome Measures

Primary Outcomes (1)

  • The trial is designed to assure that the toxicity rate is acceptably low to warrant further study of the cell vaccine in efficacy trials.

    June 2011

Study Arms (2)

control dendritic cells

EXPERIMENTAL

autologous dendritic cells that are not treated

Biological: control dendritic cells

AS ODN dendrtitic cells

EXPERIMENTAL

autologous dendritic cells treated ex vivo with the mixture of the antisense oligonucleotides

Biological: Diabetes-suppressive dendritic cell vaccine

Interventions

Diabetes-suppressive dendritic cell vaccineBIOLOGICAL

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.

Also known as: diabetes-suppressive dendritic cells
AS ODN dendrtitic cells
control dendritic cellsBIOLOGICAL

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.

control dendritic cells

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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)
  • +12 more criteria

You may not qualify if:

  • 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
  • Pregnancy
  • History of radiation therapy, immunotherapy, or chemotherapy
  • Breastfeeding
  • The following therapies cannot be administered while patients are undergoing treatment on this protocol:
  • radiation therapy
  • chemotherapy
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

  • Harnaha J, Machen J, Wright M, Lakomy R, Styche A, Trucco M, Makaroun S, Giannoukakis N. Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells. Diabetes. 2006 Jan;55(1):158-70.

    PMID: 16380489RESULT

  • Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol. 2004 Oct 1;173(7):4331-41. doi: 10.4049/jimmunol.173.7.4331.

    PMID: 15383562RESULT

  • Phillips BE, Garciafigueroa Y, Engman C, Trucco M, Giannoukakis N. Tolerogenic Dendritic Cells and T-Regulatory Cells at the Clinical Trials Crossroad for the Treatment of Autoimmune Disease; Emphasis on Type 1 Diabetes Therapy. Front Immunol. 2019 Feb 6;10:148. doi: 10.3389/fimmu.2019.00148. eCollection 2019.

    PMID: 30787930DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Massimo Trucco, M.D.

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 7, 2007

First Posted

March 9, 2007

Study Start

March 1, 2007

Primary Completion

January 1, 2012

Study Completion

February 1, 2016

Last Updated

February 15, 2016

Record last verified: 2016-02

Locations

US(1)