Type 1 Diabetes MellitusPhase 2NCT00315614

Islet Cell Transplantation Alone and CD34+ Donor Bone Marrow Cell Infusion in Type 1 Diabetes Mellitus

A Phase 2 study testing Islet Transplantation and Bone Marrow in people with Type 1 Diabetes Mellitus, run by University of Miami at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

SPECIFIC AIMS: To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation. To induce a state of donor specific tolerance and eliminate the need for continuous immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells with islets… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Type 1 Diabetes Mellitus
What is being tested?: Islet Transplantation and Bone Marrow
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: Dec 2000to Dec 2010
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients between 18 and 65 years of age
Patients with type 1 diabetes mellitus for more than 5 years duration
One or more of the following:
Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer without symptoms and/or hypoglycemic episodes requiring assistance from either family, glucagon administration or emergency services
Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of ketoacidosis) despite intensive insulin therapy
Progressive complications of type 1 diabetes mellitus
Body Mass Index (BMI) ≤26

Who cannot join

Untreated proliferative diabetic retinopathy;
HbA1C > 12%;
Insulin requirement > 1.0u/kg/d
Stimulated or basal C-peptide > 0.3 ng/ml
Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl;
Macroalbuminuria > 300mg albumin in 24 hours

Show all 29Show fewer

Presence of panel reactive antibodies > 20%;
Previous/concurrent organ transplantation (except failed islet cell transplantation);
Any medical condition requiring chronic use of steroids;
Malignancy or previous malignancy (except non-melanomatous skin cancer);
X-ray evidence of pulmonary infection;
Active infections;
Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided)
Active peptic ulcer disease,
Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound;
Serological evidence of HIV, HBV (HBsAg+ and/or HBcAb+ and/or HBsAb+ without evidence of vaccination), HTLV-1 or HCV;
Negative serology for Epstein Barr virus (EBV) or evidence of acute infection (IgM>IgG);
Abnormal liver function test;
Anemia (hemoglobin <12.0 g/dl);
Hyperlipidemia (fasting total cholesterol >240mg/dl and/or fasting triglycerides >200mg/dl and/or fasting LDL cholesterol>140mg/dl);
Body Mass Index above 26 and/or weight >80kg;
Prostate specific antigen (PSA) > 4 ng/ml;
Unstable cardiovascular status (including positive stress echocardiography if >age 35);
Active alcohol or substance abuse;
Sexually active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable);
Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate.
Any condition or any circumstances that makes it unsafe to undergo an islet cell transplant.
History of previous transplant or previous bone marrow infusion.
Persistent leucopenia (white blood cell count <3,000/mm3

Trial locations and contacts

1 site in 1 country.

United States1 site

Diabetes Research Institute
Miami, Florida, 33136

Other trials in United States

About this study

Official title: Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen

SPECIFIC AIMS:

To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation.
To induce a state of donor specific tolerance and eliminate the need for continuous immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells with islets and utilization of the monoclonal antibody Campath-1H for induction of Immunosuppression.
To assess long-term function of successful islet cell transplants in patients with Type 1 diabetes mellitus.
To determine whether the natural history of the microvascular, macrovascular and neuropathic complications are altered following successful transplantation of islet

Read the detailed description

In our current protocol (IRB #2000/0024) the immunosuppressive regimen, comprised of induction with daclizumab and maintenance therapy with sirolimus and tacrolimus, has been combined with the infusion of CD34+ enriched donor bone marrow stem cells in an attempt to create a chimeric state and hence induce donor tolerance. This strategy was tested by evaluating graft survival following the removal of all immunosuppressive medication after one year.

Conditions: Type 1 Diabetes Mellitus
Being tested: Islet Transplantation and Bone Marrow
Keywords: Islet Transplantation
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.

Islet Transplantation and Bone MarrowBiological
Also called Islet, type 1 DM, Bone marrow
Islet transplantation and CD34 Bone Marrow infusion in subjects with type 1 diabetes.

Study groups in NCT00315614
Study group	Role	What they receive
Islet Transplantation and Bone Marrow	Experimental	Administration of islets and infusion of CD34 enriched Bone Marrow cells in subjects with type 1 diabetes, impaired awareness of hypoglycemia and severe hypoglycemia. Receives: Biological: Islet Transplantation and Bone Marrow

What is being measured

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

The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.
Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
Measured: for the duration of islet graft function
A Reduction or Absence of Rejection Episodes
Number of rejection episodes after transplantation. Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
Measured: for the duration of islet graft function

Secondary outcomes (2)

Number of Subjects With Basal C-peptide Greater Than 0.5 ng/ml
Number of subjects with basal C-peptide greater than 0.5 ng/ml prior to weaning of immunosuppression;
Measured: for the duration of islet graft function
Number of Subjects With Reduction of Severe Hypoglycemia and Improvement in Hypoglycemia Awareness
Number of subjects with reduction of episodes of severe hypoglycemia and the presence of awareness of hypoglycemia
Measured: for the duration of islet graft function

Timeline

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

Dec 2000Dec 2010

First posted18 Apr 2006 (estimated)
Study startDec 2000
Primary completionDec 2010
Study completionDec 2010

Why it stopped: We did not achieve a tolerogenic profile. Subjects withdrew from protocol and enrolled in other islet transplant trials.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by University of MiamiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00315614
Sponsor's protocol ID: 2000/0024
Other IDs: R01DK056953
Status last verified: Mar 2017
First submitted: 14 Apr 2006
Last updated: 4 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No: Single arm few subjects.

Publications

Tharavanij T, Betancourt A, Messinger S, Cure P, Leitao CB, Baidal DA, Froud T, Ricordi C, Alejandro R. Improved long-term health-related quality of life after islet transplantation. Transplantation. 2008 Nov 15;86(9):1161-7. doi: 10.1097/TP.0b013e31818a7f45.
PubMed 19005394

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Adapting FAMS to Optimize CGM Use Among Emerging Adults With Type 1 Diabetes
Type 1 Diabetes
Not yet recruiting
Outpatient Pramlintide Study
Type 1 Diabetes
Active, not recruitingPhase 2
Frexalimab in Preservation of Endogenous Insulin Secretion Compared to Placebo in Adults and Adolescents on Top of Insulin Therapy (FABULINUS)
Type 1 Diabetes Mellitus
Active, not recruitingPhase 2
Probiotics in Newly Diagnosed T1D
Type 1 Diabetes, Type1diabetes
Recruiting
Differentiating Heart Disease Between Adult-onset Autoimmune and Type 2 Diabetes
Diabete Mellitus, Autoimmune Diabetes

All Type 1 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen
ClinicalTrials.gov ID: NCT00315614
Acronym / sponsor ID: 2000/0024
Conditions: Type 1 Diabetes Mellitus
Keywords: Islet Transplantation
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: We did not achieve a tolerogenic profile. Subjects withdrew from protocol and enrolled in other islet transplant trials.
Enrolment: 3 participants (actual)
Lead sponsor: University of MiamiUniversity, hospital or other
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Diabetes Research Institute Foundation
Study start: Dec 2000
Primary completion: Dec 2010 (actual)
Study completion: Dec 2010 (actual)
First posted: 18 Apr 2006 (estimated)
Results: Posted 10 Feb 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

SPECIFIC AIMS:

To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation.
To induce a state of donor specific tolerance and eliminate the need for continuous immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells with islets and utilization of the monoclonal antibody Campath-1H for induction of Immunosuppression.
To assess long-term function of successful islet cell transplants in patients with Type 1 diabetes mellitus.
To determine whether the natural history of the microvascular, macrovascular and neuropathic complications are altered following successful transplantation of islet

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Islet Transplantation and Bone Marrow	Experimental	Biological: Islet Transplantation and Bone MarrowAdministration of islets and infusion of CD34 enriched Bone Marrow cells in subjects with type 1 diabetes, impaired awareness of hypoglycemia and severe hypoglycemia.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Patients between 18 and 65 years of age
Patients with type 1 diabetes mellitus for more than 5 years duration
One or more of the following:
Body Mass Index (BMI) ≤26

Key exclusion criteria (29 listed)

Untreated proliferative diabetic retinopathy;
HbA1C > 12%;
Insulin requirement > 1.0u/kg/d
Stimulated or basal C-peptide > 0.3 ng/ml
Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Islet Transplantation and Bone MarrowAlso: Islet, type 1 DM, Bone marrowIslet transplantation and CD34 Bone Marrow infusion in subjects with type 1 diabetes.	Biological	Islet Transplantation and Bone Marrow

Primary outcome

The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.
Time frame: for the duration of islet graft function
Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
A Reduction or Absence of Rejection Episodes
Time frame: for the duration of islet graft function
Number of rejection episodes after transplantation. Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.

2 secondary outcomes

Number of Subjects With Basal C-peptide Greater Than 0.5 ng/ml
Time frame: for the duration of islet graft function
Number of Subjects With Reduction of Severe Hypoglycemia and Improvement in Hypoglycemia Awareness
Time frame: for the duration of islet graft function

Results and safety

Results posted to the registry on 10 Feb 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Islet Transplantation and Bone Marrow	3	3

Primary outcome: The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.

Time frame: for the duration of islet graft function

Measure	Islet Transplantation and CD34 Bone Marrow n = 0
Value	0

Population analysed: IImmunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint. No data available to analyze.

Primary outcome: A Reduction or Absence of Rejection Episodes

Time frame: for the duration of islet graft function

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Islet Transplantation and CD34 Bone Marrow	2 of 3 (66.7%)	3 of 3 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 19005394Tharavanij T, Betancourt A, Messinger S, Cure P, Leitao CB, Baidal DA, Froud T, Ricordi C, Alejandro R. Improved long-term health-related quality of life after islet transplantation. Transplantation. 2008 Nov 15;86(9):1161-7. doi: 10.1097/TP.0b013e31818a7f45.
Diabetes Research Institute web siteLink provided by the sponsor.
Individual participant dataSharing planned: No. Single arm few subjects.

Related trials for Type 1 Diabetes Mellitus

Active, not recruiting
Adapting FAMS to Optimize CGM Use Among Emerging Adults With Type 1 Diabetes
Type 1 Diabetes
Not yet recruiting
Outpatient Pramlintide Study
Type 1 Diabetes
Active, not recruitingPhase 2
Frexalimab in Preservation of Endogenous Insulin Secretion Compared to Placebo in Adults and Adolescents on Top of Insulin Therapy (FABULINUS)
Type 1 Diabetes Mellitus
Active, not recruitingPhase 2
Probiotics in Newly Diagnosed T1D
Type 1 Diabetes, Type1diabetes
Recruiting
Differentiating Heart Disease Between Adult-onset Autoimmune and Type 2 Diabetes
Diabete Mellitus, Autoimmune Diabetes

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rodolfo Alejandro, MD principal investigator

Diabetes Research Institute University of Miami

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Islet Transplantation and Bone Marrow in people with Type 1 Diabetes Mellitus, run by University of Miami 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 7 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: stopped early, as of the sponsor's last update on 4 Apr 2017. 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 10 Feb 2014). 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 Achievement of Persistent Islet Function Following Cessation of Immunosuppression. (time frame: for the duration of islet graft function). The study lists 2 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 NCT00315614, which also lists 1 linked publication.

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 4 Apr 2017.