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Kidney TransplantPhase 2NCT02464878

Multicenter Trial of the Effect of AAT on Islet Transplant Engraftment and Durability After Renal Transplant

A Phase 2 study testing Alpha 1-Antitrypsin, Islet Transplantation and Thymoglobulin in people with Kidney Transplant and Type 1 Diabetes, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients meeting the study entry criteria will receive 1-3 infusion(s) of in vitro cultured islets. Patients will receive three times a week AAT infusions in the peri-transplant period for three weeks. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Kidney Transplant, Type 1 Diabetes
What is being tested?
Alpha 1-Antitrypsin, Islet Transplantation and Thymoglobulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Jan 2017to Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 subjects age 18 to 70 years.
  • Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
  • Subjects must have one of the following payment mechanisms in place:
  • Medicare,
  • A third-party insurer who agrees, via pre-authorization, to pay for participation in the study, or
  • Another mechanism of payment (self-pay, hospital, university, donations, etc.) for participation in the study.
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  • Clinical history compatible with T1D with disease onset < 40 years of age and insulin-dependence for ≥ 5 years at the time of enrollment.
  • Absent stimulated c-peptide (< 0.3 ng/mL) in response to a MMTT [Boost® 6 mL/kg body weight (BW) to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost®] measured at 60 and 90 min after start of consumption.
  • Subjects who are ≥ 3 months post-renal 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).
  • Stable renal function as defined by a creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation, until rejection, obstruction or infection is ruled out.
  • Subjects who meet one of the options in the following criterion are eligible for transplantation:
  • Reduced awareness of hypoglycemia manifested by a Clarke score of 4 or more measured upon study enrollment and at least one episode of severe hypoglycemia in the 12 months prior to study enrollment.
  • A subject must have a reduced awareness of hypoglycemia manifested by a Clarke score of 4 or more and at least 1 episode of severe hypoglycemia;
  • Any subject not meeting the hypoglycemia option must have an HbA1c > 7.5%.

Who cannot join

  • Weight more than 100 kg or body mass index (BMI) > 33 kg/m2.
  • Insulin requirement of >1.0 U/kg/day or, > 60 U/day total, or <15 U/day.
  • Other (non-kidney) organ transplants except prior failed pancreatic graft where graft failure is attributed to thrombosis within the first 4 weeks or to other technical reasons that require graft pancreatectomy; with the graft pancreatectomy occurring more than 6 months ago.
  • Untreated or unstable proliferative diabetic retinopathy.
  • Blood Pressure: SBP > 160 mmHg or DBP >100 mmHg despite treatment with antihypertensive agents.
  • 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) equation1. Strict vegetarians (vegans) will be excluded only if their estimated GFR is ≤ 35 mL/min/1.73 m2.
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  • 7. Proteinuria (albumin/creatinine ratio or ACr > 300mg/g) of new onset since kidney transplantation.
  • Calculated panel-reactive anti-HLA antibodies > 50%. Subjects with calculated panel reactive anti-HLA antibodies ≤ 50% will be excluded if any of the following are detected:
  • Positive cross-match,
  • Islet donor-directed 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, or
  • Antibodies to the renal donor (i.e. presumed de novo).
  • 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.
  • Presence or history 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 at time of screening or previous kidney transplant.
  • Invasive aspergillus, histoplasmosis, and coccidoidomycosis infection within the last year.
  • Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
  • Known active alcohol or substance abuse.
  • Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g. warfarin) after islet transplantation (low-dose aspirin treatment [325 mg PO] is allowed) or subjects with international normalized ratio (INR) > 1.5. The use of Plavix is allowed only in conjunction with mini- laparotomy procedure at the time of islet transplant.
  • Severe co-existing cardiac disease, characterized by any one of these conditions:
  • Recent MI (within past 6 months);
  • Evidence of ischemia on functional cardiac exam within the last year;
  • Left ventricular ejection fraction < 30%; or
  • Valvular disease requiring replacement with prosthetic valve.
  • Persistent serum glutamic-oxaloacetic transaminase (SGOT [AST]), serum glutamate pyruvate transaminase (SGPT [ALT],) alkaline phosphatase or total bilirubin, with values > 1.5 times normal upper limits will exclude a subject.
  • Active infections (except mild skin and nail fungal infections).
  • Acute or chronic pancreatitis.
  • Active peptic ulcer disease, symptomatic gallstones, or portal hypertension.
  • Use of any investigational agents within 4 weeks of enrollment.
  • Administration of live attenuated vaccine(s) within 2 months of enrollment.
  • Any medical condition that, in the opinion of the investigator, will interfere with the safe participation in the trial. (Cancer screenings should be performed per current American Cancer Society guidelines).
  • Positive screen for BK virus by polymerase chain reaction (PCR) performed at time of screening.
  • A kidney transplant patient with type 1 diabetes who has an HbA1c < 7.5 and no history of severe hypoglycemia.
  • Selective or severe IgA deficiency (levels < 5-7 mg/dL)
  • AAT deficiency (defined as < 1.0ng/mg AAT)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Patients meeting the study entry criteria will receive 1-3 infusion(s) of in vitro cultured islets. Patients will receive three times a week AAT infusions in the peri-transplant period for three weeks.

Being tested
Alpha 1-Antitrypsin, Islet Transplantation, Thymoglobulin, Basiliximab, Etanercept
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

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

  • Alpha 1-AntitrypsinDrug

    Also called Glassia

    Patients will receive three times a week AAT infusions in the peri-transplant period for three weeks.

  • Islet TransplantationProcedure or surgery

  • ThymoglobulinDrug

    Also called Antithymocyte Globulin

    Patients will receive a total of 5 doses between Day -2 and Day +2

  • BasiliximabDrug

    Basiliximab will be used for subsequent transplants.

  • EtanerceptDrug

    Also called Enbrel

    Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.

Study groups in NCT02464878
Study groupRoleWhat they receive
Main study treatmentOtherNot described
Receives: Drug: Alpha 1-Antitrypsin; Procedure: Islet Transplantation; Drug: Thymoglobulin; Drug: Basiliximab; Drug: Etanercept

What is being measured

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

  1. The Proportion of GLASSIA Versus Control CIT06 Subjects Achieving Insulin Independence After First Infusion of Single Donor Islets.

    Insulin Independence examined 75 days after 1st infusion; subject considered to be insulin independent if they are able to titrate off insulin therapy for <1 week AND all of the following are met:

    1. one HbA1c level, one fasting serum glucose level, and a Mixed Meal Tolerance Test (MMTT) documented within the visit window at Day 75 (Day 70-80) and 7 days of blood sugar and insulin readings are documented within +/- 7 days of the visit window (Day 63-87);
    2. HbA1c </= 6.5% or a >/= 2.5% decrease from baseline (within 91 days prior to transplant);
    3. fasting capillary glucose level should not exceed 140 mg/dL more than 3 times in 7 consecutive days;
    4. post-prandial serum glucose </= 180 mg/dL at 90 minutes during MMTT;
    5. fasting serum glucose level </= 126 mg/dL; (6) at least one MMTT fasting or stimulated c-peptide >/= 0.5 ng/mL

    Measured: Day 75

Secondary outcomes (8)

  1. The Proportion of GLASSIA Treated Versus Control CIT06 Subjects Who Are Insulin Independent After 1 or More Islet Infusions

    Subject considered to be insulin independent if they are able to titrate off insulin therapy for <1 week AND all of the following are met:

    1. one HbA1c level, one fasting serum glucose level, and a Mixed Meal Tolerance Test (MMTT) documented within the visit window of time frame, noted below, and 7 days of blood sugar and insulin readings are documented within +/- 7 days of the visit window;
    2. HbA1c </= 6.5% or a >/= 2.5% decrease from baseline (within 91 days prior to transplant);
    3. fasting capillary glucose level should not exceed 140 mg/dL more than 3 times in 7 consecutive days;
    4. post-prandial serum glucose </= 180 mg/dL at 90 minutes during MMTT;
    5. fasting serum glucose level </= 126 mg/dL;
    6. at least one MMTT fasting or stimulated c-peptide >/= 0.5 ng/mL

    Measured: 1 year after the first islet infusion, 1 year after the last islet infusion, 2 years after the first islet infusion, 2 years after the last islet infusion

  2. The Proportion of GLASSIA Treated Versus CIT06 Control Subjects With Both an HbA1c ≤ 6.5% AND an Absence of Severe Hypoglycemic Events

    Number of subjects with both an HbA1c </= 6.5% and no severe hypoglycemic events at specified timepoints; data utilized for measure were HbA1c levels and number of severe hypoglycemic events.

    Measured: From Day 28 to Day 365 after the first islet transplant, From Day 28 to Day 730 after the first islet transplant.

  3. The Proportion of GLASSIA Treated Versus Control Subjects With Both an HbA1c < 7.0% AND Free of Severe Hypoglycemic Events

    Subjects with an HbA1c <7.0% and free of severe hypoglycemic events at specified timepoints; data utilized were HbA1c levels and number/absence of severe hypoglycemic events

    Measured: From Day 28 to Day 365 after the first islet transplant, From Day 28 to Day 730 after the first islet transplant.

  4. The Proportion of GLASSIA Treated Versus Control CIT06 Subjects A Reduction in HbA1c of 1 Point AND an Absence of Severe Hypoglycemia

    Subjects with a reduction in HbA1c of 1 point and no severe hypoglycemia at specific timepoints. Data utilized were HbA1c numbers at specified timepoints and absence of any severe hypoglycemic events

    Measured: From Day 28 to Day 365 after the first islet transplant, From Day 28 to Day 730 after the first islet transplant.

  5. The Change in Clarke Score From Baseline in GLASSIA Treated Versus Control CIT06 Subjects

    Clarke Score is a 7 question patient report of hypoglycemia awareness. Answers provide a rating of either A (aware) or R (reduced). Four or more R ratings suggest impaired hypoglycaemia awareness; < or equal to 2 = normal awareness, 3=borderline. A higher Clarke Score indicates reduced awarness.

    Measured: 1 year and 2 years after the first islet transplant

  6. The Proportion of Subjects Receiving a Second Islet Transplant Comparing GLASSIA Treated Versus Control CIT06 Subjects

    Subjects requiring a 2nd islet infusion at specified timepoints; data utilized were the number of patients who were not successful at gaining and maintaining insulin independence following the 1st infusion and required a 2nd infusion/transplant of islets.

    Measured: 1 year and 2 years following the first and last islet transplant(s)

  7. The Proportion of Subjects Receiving a Third Islet Transplant Comparing GLASSIA Treated Versus Control CIT06 Subjects

    Number of subjects requiring a 3rd islet infusion. Data utilized were the number of patients require a 3rd transplant/infusion of islets due to continued requirement of insulin during study participation.

    Measured: 1 year and 2 years following the first and last islet transplant(s)

  8. Cardiovascular Events [Death, Cerebrovascular Accident (CVA), Myocardial Infarction (MI)] and Changes in Atherogenic Profile for GLASSIA Treated Versus Control Subjects

    Subjects experience of cardiovascular events and changes in atherogenic profile were examined for the timepoints listed below. Data utilized were baseline lipid labs (triglycerides, total cholesterol, HDL, LDL, and Non-HDL Cholesterol) and lipid labs taken at specified timepoints. An improvement would be an overall improvement of the lipid profile (e.g. reduction in non-HDL cholesterol/overall cholesterol, decrease in LDL, increase in HDL, etc.). Due to the COVID-19 pandemic and increased risk faced by transplant/immunosuppressed individuals, some lipid labs were not collected and data has been indicated as NA due to reduction in sample collection/prioritizing safety labs for subjects.

    Measured: 1 year and 2 years following the first and last islet transplant(s)

Timeline

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

  1. First posted8 Jun 2015 (estimated)
  2. Study startJan 2017
  3. Primary completionNov 2022
  4. Study completionDec 2022

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02464878
Sponsor's protocol ID
Islet after Kidney - AAT
Status last verified
Nov 2023
First submitted
3 Jun 2015
Last updated
22 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpha 1-Antitrypsin, Islet Transplantation and Thymoglobulin in people with Kidney Transplant and Type 1 Diabetes, run by Massachusetts General Hospital 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 14 inclusion and 34 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: finished, as of the sponsor's last update on 22 Dec 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Proportion of GLASSIA Versus Control CIT06 Subjects Achieving Insulin Independence After First Infusion of Single Donor Islets. (time frame: Day 75). 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 NCT02464878.

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 22 Dec 2023.

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