AzTrials
AzTrials

Islet TransplantationPhase 1NCT05973734

Islet Transplantation With Recipient T-Reg Cells or Deceased Donor Vertebral Bone Marrow Therapy

A Phase 1 study testing Infusion of recipient T regulatory cell and Infusion of concomitant Donor Derived Vertebral Bone Marrow in people with Islet Transplantation, run by Stanford University at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this clinical trial is to learn if patients who have brittle type 1 diabetes receiving an islet transplantation will have better control of their sugars if they also receive one of 2 types of immune cells along with the islet transplant. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Islet Transplantation
What is being tested?
Infusion of recipient T regulatory cell and Infusion of concomitant Donor Derived Vertebral Bone Marrow
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
15 Apr 2024to Dec 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female patients age 18 to 70 years of age.
  • Ability to provide written informed consent.
  • Mentally stable and able to comply with the procedures of the study protocol.
  • Clinical history compatible with T1D with onset of disease at < 45 years of age, insulin- dependence for ≥ 5 years at the time of enrollment, or a sum of patient age and insulin dependent diabetes duration of ≥ 28.
  • Absence of stimulated C peptide (< 0.3 ng/mL) in response to a mixed meal tolerance test measured at 60 and 90 minutes after the start of consumption
  • Involvement in intensive diabetes management defined as self-monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the 12 months prior to study enrollment.
Show all 15Show fewer
  • At least two episodes of severe hypoglycemia in the 12 months prior to study enrollment.
  • Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR a HYPO score greater than or equal to the 90th percentile (1047) during the screening period and within the last 6 months prior to randomization.
  • Women of childbearing potential may be enrolled if a pregnancy test is negative, and they agree to the use of 2 forms of contraception from Screening to the end of the study. Males must agree to use 2 forms of contraception from Screening to the end of the study if their partners are of childbearing potential.
  • Acceptable methods of birth control which must be used together are:
  • Oral contraceptive and condom (combination oral contraceptives containing the second- generation progestin (levonorgestrel) and <30 μg of estrogen should be utilized),
  • IUD and condom,
  • Diaphragm with spermicide and condom
  • Subject must complete training on how to use the Tandem X2 pump with Control IQ technology by a certified Diabetes Educator or physician. Patients must complete at least 2 hour training to the satisfaction of the educator and show proficiency and understanding in its use as judged by the educator.
  • Patients with prior kidney transplantation on immunosuppressive medications are eligible provided they meet all eligibility criteria above excluding the need for hypoglycemia unawareness. Patients should not be candidates for solid organ pancreas transplant or have declined the surgical option.

Who cannot join

  • Body mass index (BMI) >30 kg/m2 or patient weight ≤50kg.
  • Insulin requirement of >1.0 IU/kg/day or <15 U/day. 3. HbA1c >10%.
  • Treatment with any anti-diabetic medication other than insulin within 4 weeks of Screening
  • Untreated proliferative diabetic retinopathy.
  • Blood Pressure: SBP >180 mmHg or DBP >100 mmHg on optimal treatment.
  • Estimated glomerular filtration rate of <50 mL/min/1.73m2.
Show all 29Show fewer
  • Presence or history of macroalbuminuria (>500mg/g creatinine).
  • Presence or history of panel-reactive anti-HLA antibodies >50%. Negative cross- match by flow cytometry and no DSA to organ donor by standard methods.
  • 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 participants: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception
  • Presence of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
  • Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
  • Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment.
  • Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
  • Known active alcohol or substance abuse.
  • Baseline Hb below the lower limits of normal; neutropenia (<1,500/7L), or thrombocytopenia (platelets <100,000/7L).
  • Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after islet transplantation (low-dose aspirin treatment is allowed) or patients with an international normalized ratio (INR) >1.5.
  • Severe co-existing cardiac disease, characterized by any one of these conditions:
  • recent myocardial infarction (within past 6 months).
  • evidence of uncorrectable ischemia on functional cardiac exam within the last year.
  • left ventricular ejection fraction <30%.
  • Persistent elevation of liver function tests at the time of study entry. Persistent serum glutamic-oxaloacetic transaminase (SGOT [AST]), serum glutamate pyruvate transaminase (SGPT [ALT]), or total bilirubin, with values > 1.5 times normal upper limits will exclude a patient.
  • Acute or chronic pancreatitis.
  • Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
  • Use of any investigational agents within 4 or more weeks of enrollment, depending upon the pharmacokinetics of the investigational agent and durability of changes with treatment in immune function or glycemic regulation.
  • Administration of live attenuated vaccine(s) within 2 months of enrollment.
  • Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.
  • A previous islet transplant.
  • History of medical non-adherence or poor social support.
  • Individuals with selective IgA deficiencies (IgA level less than 15 mg/dL) who have known antibody against IgA.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

  • Stanford University

    Palo Alto, California, 94305

Other trials in United States

About this study

Official title: Clinical Islet Transplantation With Apheresis, Isolation and Reintroduction of Recipient Regulatory T Cells or Administration of Deceased Donor Vertebral Bone Marrow in Type 1 Diabetes

The goal of this clinical trial is to learn if patients who have brittle type 1 diabetes receiving an islet transplantation will have better control of their sugars if they also receive one of 2 types of immune cells along with the islet transplant. The participants will receive either their own immune cells, called regulatory T cells, or immune cells from the bone marrow of the islet donor.

Read the detailed description

Islet transplantation success remains limited by the immediate loss of islet after transplantation, rejection, and side effect from immunosuppression. Preclinical animal models provide evidence that donor bone marrow cells OR regulatory T cells infused at the time of islet transplantation can improve the survival of islets after transplantation and reduce the need for immunosuppression. The purpose of this study is to evaluate the feasibility and safety of combining an islet transplant with the recipient's Tregs OR deceased donor bone marrow cells in patients with brittle type 1 diabetes.

Being tested
Infusion of recipient T regulatory cell, Infusion of concomitant Donor Derived Vertebral Bone Marrow

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Infusion of recipient T regulatory cellBiological

    Patients will undergo a single apheresis collection with a target total blood volume of 20-30 L and the collected cells used as the source of purified Tregs to be infused following the islet transplantation. In the event a patient is unable to meet the collection target, a second collection may be performed.

  • Infusion of concomitant Donor Derived Vertebral Bone MarrowBiological

    The cells from the donor VB and spleen are processed under cGMP conditions and released for infusion after the respective recipient has undergone transplant and conditioning. Under this protocol, the donor's VB will be obtained at the same time as the pancreatic islets and will be the source of HSC for infusion with the intent to establish immune tolerance to the donor's pancreatic islet cells. Subjects will receive one infusion of allogeneic cadaveric islets. Subjects will receive induction therapy with ATG and Belatacept and maintenance immunosuppression with Tacrolimus Extended-release tablets (Envarsus XR) and Mycophenolate Mofetil (MMF). After islet transplantation, the VBM cells will be infused in one time window: on day 0-1. Subjects will undergo closed-loop insulin pump glucose control peri-transplant.

Study groups in NCT05973734
Study groupRoleWhat they receive
Recipient T Regulatory CellExperimentalT regulatory cells prior to islet transplantation, induction therapy with ATG and Belatacept and maintenance immunosuppression with Tacrolimus Extended-release tablets (Envarsus XR) and Mycophenolate Mofetil (MMF).
Receives: Biological: Infusion of recipient T regulatory cell
Donor Derived Vertebral Bone MarrowExperimentalDeceased donor vertebral bone marrow (VBM) cells, induction therapy with ATG and Belatacept and maintenance immunosuppression with Tacrolimus Extended-release tablets (Envarsus XR) and Mycophenolate Mofetil (MMF).
Receives: Biological: Infusion of concomitant Donor Derived Vertebral Bone Marrow

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of Grade 3 to 5 cytokine release syndrome / acute infusion reaction after Treg administration infusion reaction after Treg administration

    Grade 3 to 5 cytokine release syndrome / acute infusion reaction after Treg administration infusion reaction after Treg administration

    Measured: within 3 months

  2. Occurrence of grade 4 or greater adverse events of islet transplantation

    Adverse event grade 4 or greater

    Measured: Within two years

  3. Number of patients who receive Treg infusions (Arm1) or Donor Derived Vertebral Bone Marrow (Arm2) and islet transplantation (feasibility)

    Number of patients who received planned Treg or Donor Bone Marrow

    Measured: Within two years

Secondary outcomes (8)

  1. HbA1c ≤6.5%

    HbA1c ≤6.5%

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  2. Absence of severe hypoglycemic events

    Absence of severe hypoglycemic event , requiring intervention by other person than the patient

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  3. Decrease of insulin mean requirements (u/kg) from prior to transplantation by 50% of total daily dose

    Reduction of exogenous insulin requirement by 50% from baseline

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  4. Clarke hypoglycemia severity (HYPO) score less than 2 (0 to >4, >4 indicate severe hypoglycemia unawareness)

    Improvement of Clarke score to less than 2

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  5. Basal C-peptide at levels e >0.5 ng/mL (>0.17 nmol/L) fasting or stimulated.

    C-petide production from islet transplant assessment

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  6. Target of glucose variability and hypoglycemia duration derived from the CGMS <Standard Deviation and Coefficient targets>

    Monitoring of glucose control 24h sensor monitoring

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  7. Measurement of donor Specific Antibody, cPRA

    Single bead luminex anti HLA class 1 and 2 assay

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

  8. Quality of life (QOL) assessment

    QOL questionnaire SF-12 (0-100, higher score is better outcome)

    Measured: assessed at 6, 12 and 24 months post-islet transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2023
  2. Study start15 Apr 2024
  3. Primary completionDec 2030 (estimated)
  4. Study completionDec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
All patients are planned to receive an islet transplantation. The patients will also receive either Arm 1) recipient T regulatory cell infusion or arm 2) same donor vertebral body derived bone marrow cell infusion. Attribution to either arm will be based on the availability of either cell product in specific cases.
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05973734
Sponsor's protocol ID
58350
Status last verified
Jun 2026
First submitted
14 Jun 2023
Last updated
8 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ryan EA, Shandro T, Green K, Paty BW, Senior PA, Bigam D, Shapiro AM, Vantyghem MC. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes. 2004 Apr;53(4):955-62. doi: 10.2337/diabetes.53.4.955.

    PubMed 15047610

  • Kessler L, Passemard R, Oberholzer J, Benhamou PY, Bucher P, Toso C, Meyer P, Penfornis A, Badet L, Wolf P, Colin C, Morel P, Pinget M; GRAGIL Group. Reduction of blood glucose variability in type 1 diabetic patients treated by pancreatic islet transplantation: interest of continuous glucose monitoring. Diabetes Care. 2002 Dec;25(12):2256-62. doi: 10.2337/diacare.25.12.2256.

    PubMed 12453970

  • Streja D. Can continuous glucose monitoring provide objective documentation of hypoglycemia unawareness? Endocr Pract. 2005 Mar-Apr;11(2):83-90. doi: 10.4158/EP.11.2.83.

    PubMed 15901522

  • Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.

    PubMed 8366922

  • Hirsch IB. Insulin analogues. N Engl J Med. 2005 Jan 13;352(2):174-83. doi: 10.1056/NEJMra040832. No abstract available.

    PubMed 15647580

  • Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003 Jun;26(6):1902-12. doi: 10.2337/diacare.26.6.1902.

    PubMed 12766131

  • Gold AE, MacLeod KM, Frier BM. Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care. 1994 Jul;17(7):697-703. doi: 10.2337/diacare.17.7.697.

    PubMed 7924780

  • Larsen JL. Pancreas transplantation: indications and consequences. Endocr Rev. 2004 Dec;25(6):919-46. doi: 10.1210/er.2002-0036.

    PubMed 15583023

  • Cryer PE, Fisher JN, Shamoon H. Hypoglycemia. Diabetes Care. 1994 Jul;17(7):734-55. doi: 10.2337/diacare.17.7.734. No abstract available.

    PubMed 7924788

  • Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9. doi: 10.2337/diabetes.54.7.2060.

    PubMed 15983207

  • Hering BJ, Clarke WR, Bridges ND, Eggerman TL, Alejandro R, Bellin MD, Chaloner K, Czarniecki CW, Goldstein JS, Hunsicker LG, Kaufman DB, Korsgren O, Larsen CP, Luo X, Markmann JF, Naji A, Oberholzer J, Posselt AM, Rickels MR, Ricordi C, Robien MA, Senior PA, Shapiro AM, Stock PG, Turgeon NA; Clinical Islet Transplantation Consortium. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2016 Jul;39(7):1230-40. doi: 10.2337/dc15-1988. Epub 2016 Apr 18.

    PubMed 27208344

  • Krzystyniak A, Golab K, Witkowski P, Trzonkowski P. Islet cell transplant and the incorporation of Tregs. Curr Opin Organ Transplant. 2014 Dec;19(6):610-5. doi: 10.1097/MOT.0000000000000130.

    PubMed 25304813

  • Pierini A, Iliopoulou BP, Peiris H, Perez-Cruz M, Baker J, Hsu K, Gu X, Zheng PP, Erkers T, Tang SW, Strober W, Alvarez M, Ring A, Velardi A, Negrin RS, Kim SK, Meyer EH. T cells expressing chimeric antigen receptor promote immune tolerance. JCI Insight. 2017 Oct 19;2(20):e92865. doi: 10.1172/jci.insight.92865.

    PubMed 29046484

  • Cryer PE. Banting Lecture. Hypoglycemia: the limiting factor in the management of IDDM. Diabetes. 1994 Nov;43(11):1378-89. doi: 10.2337/diab.43.11.1378.

    PubMed 7926315

  • Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000 Jul 27;343(4):230-8. doi: 10.1056/NEJM200007273430401.

    PubMed 10911004

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Infusion of recipient T regulatory cell and Infusion of concomitant Donor Derived Vertebral Bone Marrow in people with Islet Transplantation, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of Grade 3 to 5 cytokine release syndrome / acute infusion reaction after Treg administration infusion reaction after Treg administration (time frame: within 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05973734, which also lists 44 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in