Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pancreatic Islets and Parathyroid Gland Co-transplantation for Treatment of Type 1 Diabetes (PARADIGM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03977662
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : May 5, 2020
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Peter Stock, University of California, San Francisco

Brief Summary:
The primary objective is to test the hypothesis that co-transplantation of allogeneic PTG with adult pancreatic islets (derived from same deceased donor) in the IM site in people with Type 1 diabetes with functioning kidney and/or liver transplants is safe, allows islet engraftment, and leads to insulin independence.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Combination Product: Co-transplantation of PTG with pancreatic islets Phase 1 Phase 2

Detailed Description:

Single-center, open label, non-randomized safety and efficacy trial to evaluate co-transplantation of allogeneic parathyroid glands (PTG) with adult pancreatic islets (both PTG and pancreatic islets obtained from same deceased donor) in people with Type 1 diabetes in the intramuscular (IM) site with stable function of liver or kidney allografts on chronic immunosuppression.

A total of 8 patients will be enrolled in the study and followed for a minimum of 1 year up to 2 years after the last islet transplant, depending on enrollment date.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pancreatic Islets and Parathyroid Gland Co-transplantation for Treatment of Diabetes in the Intra-Muscular Site
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : January 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: PTG with adult pancreatic islet co-transplantation
People with Type 1 (c-peptide negative) diabetes with stable kidney or liver allografts on chronic immunosuppression who receive study intervention, which is co-transplantation of allogeneic parathyroid (PTG) with adult pancreatic islets in people with Type 1 diabetes in the intramuscular (IM) site
Combination Product: Co-transplantation of PTG with pancreatic islets
Co-transplantation of allogeneic parathyroid glands (PTG) with adult pancreatic islets (both PTG and pancreatic islets obtained from same deceased donor) in people with Type 1 diabetes in the intramuscular (IM) site with stable function of liver or kidney allografts on chronic immunosuppression




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Minimum of 1 year up to 2 years depending on transplant date ]
    Safety: Since this study is a pilot non-randomized safety and efficacy trial with patient enrollment limited by budgetary constraints, no direct statistical significance tests can be performed.

  2. Incidence of post-transplant infections and malignancies [ Time Frame: Minimum of 1 year up to 2 years depending on transplant date ]
    Safety: Since this study is a pilot non-randomized safety and efficacy trial with patient enrollment limited by budgetary constraints, no direct statistical significance tests can be performed.

  3. Incidence of de novo sensitization [ Time Frame: Minimum of 1 year up to 2 years depending on transplant date ]
    Safety: Since this study is a pilot non-randomized safety and efficacy trial with patient enrollment limited by budgetary constraints, no direct statistical significance tests can be performed.

  4. Incidence of Insulin independence [ Time Frame: Minimum of 1 year up to 2 years depending on transplant date ]
    Efficacy: Incidence of participants no longer using insulin


Secondary Outcome Measures :
  1. Glycemic control [ Time Frame: Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2 ]
    Assessed by measuring HbA1c using high-performance liquid chromatography

  2. Glycemic lability [ Time Frame: Day 75, Day 180, Day 270, Year 1 ]
    Assessed with the Mean Amplitude of Glycemic Excursions (MAGE) test

  3. Hypoglylcemic episodes: Clarke Survey Score [ Time Frame: Day 75, Day 180, Day 270, Year 1 ]
    The Clarke survey will be used to assess the frequency and severity of hypoglycemic episodes

  4. Hypoglylcemic episodes: Hypo Score [ Time Frame: Day 75, Day 180, Day 270, Year 1 ]
    The HYPO score will be used to assess the frequency and severity of hypoglycemic episodes

  5. Beta cell function as assessed by Mixed Meal Tolerance Test (MMTT) [ Time Frame: Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2 ]
    Results from both MMTT and FSIGT will be used to assess beta cell function

  6. Beta cell function as assessed by Insulin-Modified Frequently-Sampled Intravenous Glucose ToleranceTest (FSIGT) [ Time Frame: Day 75, Day 180, Day 270, Year 1, Year 1.5, Year 2 ]
    Results from both MMTT and FSIGT will be used to assess beta cell function



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects age 18 to 70 years of age.
  2. Subjects who are able to provide written informed consent and to comply with study procedures.
  3. Clinical history compatible with Type 1 diabetes (onset < 40 yrs old and insulin dependent for > 5 yrs at enrollment, c-peptide negative).
  4. Recipients should have absent stimulated c-peptide (< 0.3 ng/mL) in response to a (Boost® 6 mL/kg BW to a maximum of 360 mL; another equivalent product), measured at 60 and 90 min after start of consumption.
  5. Subjects who are > 6 months post-renal transplant or >6 months post-liver transplant who are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppression ([tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic, or azathioprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic ± Prednisone ≤ 10 mg/day).
  6. Stable renal function as defined by a creatinine of no more than one third greater than the average creatinine determination performed in the 6 previous months prior to islet transplant, as well as absence of a rejection episode in the 6 months prior to islet transplant
  7. Stable liver function tests as defined by: SGOT (AST), SGPT (ALT), alkaline phosphatase values < 1.5, or total bilirubin < 1.5 times normal upper limits at time of study entry, as well as absence of a rejection episode in the 6 months prior to islet transplant

Exclusion Criteria:

  1. Presence of donor specific anti-HLA antibodies detected by Luminex Single Antigen/specificity bead assay including weakly reactive antibodies that would not be detected by a flow cross match
  2. Insulin requirement of >1.0 IU/kg/day
  3. Weight more than 100 kg or body mass index (BMI) > 30 kg/m2.
  4. Primary hyperparathyroidism OR secondary hyperparathyroidism
  5. Untreated or unstable proliferative diabetic retinopathy.
  6. Blood Pressure: SBP > 180 mmHg or DBP >100 mmHg despite treatment with antihypertensive agents.
  7. Calculated GFR of ≤ 40 mL/min/1.73 m2 using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) equation, as well as presence of a rejection episode in the 6 months prior to islet transplant
  8. Elevated liver function tests as defined by: SGOT (AST), SGPT (ALT), alkaline phosphatase values > 1.5, or total bilirubin >1.5 times normal upper limits at time of study entry, as well as presence of a rejection episode in the 6 months prior to islet transplant
  9. Proteinuria (albumin/creatinine ratio or ACr > 300mg/g) of new onset since kidney transplantation.
  10. For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo- Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
  11. Active infection including hepatitis B, hepatitis C, HIV, or TB. A positive skin test (PPD) in itself is not an exclusion and will be followed up by a Quantiferon gold assay.
  12. Negative screen for EBV IgG.
  13. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within 1 year prior to study entry.
  14. Any history of malignancy following receiving either the kidney or liver transplant, except for completely resected squamous or basal cell carcinoma of the skin
  15. Known active alcohol or substance abuse.
  16. Severe co-existing cardiac disease, characterized by any one of these conditions:

    1. Recent MI (within past 6 months),
    2. Evidence of ischemia on functional cardiac exam within the last year,
    3. Left ventricular ejection fraction < 30%,
    4. Valvular disease requiring replacement with prosthetic valve.
  17. Active infections (except mild skin and nail fungal infections).
  18. Active peptic ulcer disease or gastritis, symptomatic gallstones, or portal hypertension.
  19. Use of any investigational agents within 4 weeks of enrollment.
  20. Administration of live attenuated vaccine(s) within 2 months of enrollment.
  21. Any medical condition that, in the opinion of the investigator, will interfere with safe study completion.
  22. Positive screen for BK viremia at time of screening.
  23. Untreated hyperlipidemia - TC > 200 mg/dL, TGC > 200 mg/dL, LDL > 130 mg/dL

Information from the National Library of Medicine

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): NCT03977662


Contacts
Layout table for location contacts
Contact: Patricia Brennan, RN, PhD 415-476-3229 Patricia.Brennan@ucsf.edu

Locations
Layout table for location information
United States, California
University of California Recruiting
San Francisco, California, United States, 94143
Contact: Patricia Brennan, RN, PhD    415-476-3229    Patricia.Brennan@ucsf.edu   
Sponsors and Collaborators
Peter Stock
California Institute for Regenerative Medicine (CIRM)
Investigators
Layout table for investigator information
Principal Investigator: Peter Stock, MD, PhD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by Peter Stock, University of California, San Francisco:
Layout table for additonal information
Responsible Party: Peter Stock, Principle Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03977662    
Other Study ID Numbers: 18-26725
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases