Islets of Langerhans TransplantationPhase 2ITA-OMENNCT02803905
Islet Transplant Alone in OMENtum
A Phase 2 study testing Biological: Islet transplantation in people with Islets of Langerhans Transplantation and Diabetes Mellitus, Type 1, run by Lorenzo Piemonti at 1 site in Italy.
Trial summary
The study is a phase 2, monocentric, open-label study. The investigators will recruit 12 patients with T1D to be randomly (1:1) assigned to receive islet either into the liver through the portal venous circulation (standard procedure; arm A, n=6) or directly into the omentum (arm B, n=6). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Islets of Langerhans Transplantation, Diabetes Mellitus, Type 1
- What is being tested?
- Biological: Islet transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2016to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 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 <40 years of age, insulin-dependence for > 5 years at the time of enrollment, and a sum of subject age and insulin-dependent diabetes duration of ≥28.
- Absent stimulated c-peptide (<0.3ng/mL) in response to a MMTT
- Involvement in intensive diabetes management
- At least one episode 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; OR marked glycemic lability characterized by wide swings in BG despite optimal diabetes therapy and defined by an LI score greater than or equal to the 90th percentile (43 mmol/L2/h·wk-1) during the screening period; OR a composite of a Clarke score of 3 or less and a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) during the screening period.
Who cannot join
- Body Mass Index (BMI) >30 kg/m2 or patient weight ≤50 kg.
- Insulin requirement of >1.0 IU/kg/day or <15 U/day.
- HbA1c >10%.
- Untreated proliferative diabetic retinopathy.
- Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.
- Measured glomerular filtration rate <80 mL/min/1.73 m2.
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- Presence or history of macroalbuminuria (>300mg/g creatinine).
- Presence or history of panel-reactive anti-HLA antibodies above background by flow cytometry.
- For female subjects: Serum or urine 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.
- 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.
- Invasive aspergillus, histoplasmosis, and 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.
- Baseline Hb below the lower limits of normal at the local laboratory; lymphopenia (<1,000/µL), neutropenia (<1,500/µL), or thrombocytopenia (platelets <100,000/µL)
- A history of Factor V deficiency.
- Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients with an international normalized ratio (INR) >1.5.
- Severe co-existing cardiac disease
- Persistent elevation of liver function tests at the time of study entry.
- Symptomatic cholecystolithiasis.
- Acute or chronic pancreatitis.
- Symptomatic peptic ulcer disease.
- Hyperlipidemia despite medical therapy
- Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
- Treatment with any anti-diabetic medications other than insulin within 4 weeks of enrollment.
- Use of any investigational agents within 4 weeks of enrollment. 24. Administration of live attenuated vaccine(s) within 2 months of enrollment.
- Inflammatory bowel disease.
- History of intestinal obstructions.
- Previous major abdominal surgery.
- History of peritonitis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Monocentric, Open-label, Double-arm, Phase II Trial to Assess the Safety and Efficacy of Allogeneic Islet Cells Transplanted Into the Omentum
The study is a phase 2, monocentric, open-label study. The investigators will recruit 12 patients with T1D to be randomly (1:1) assigned to receive islet either into the liver through the portal venous circulation (standard procedure; arm A, n=6) or directly into the omentum (arm B, n=6). Patients will be selected from those eligible for islet Tx based on local practice and guidelines. Immunosuppression will consist of five doses IV infusion of rabbit Anti-thymocyte Globulin (ATG, Thymoglobulin®), starting two days prior to the islet transplant. Maintenance mycophenolate mofetil (MMF) therapy (1-2 g/day as BID dosing) will be started on Day -1 pre-transplant. Tacrolimus will be administered orally twice daily on Day 1 post-transplant to maintain a trough level of 10-12 ng/mL for 3 months, then 6-10 ng/mL thereafter. Etanercept will be given IV before the islet transplant (50 mg), and then at 25 mg (subcutaneously) on POD +3, +7 and +10.
- Being tested
- Biological: 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.
Biological: Islet transplantationBiological
This is a single procedure protocol. Only a single islet transplant will be performed in the patient. Islets can be isolated from more than one pancreas donor. The final islet product is a sterile suspension of ≥70% viable, ≥30% pure, allogeneic islets. A minimum of 5000 IEQ/KG will be transplanted. Although this study is a single dose protocol, islet transplant recipients with partial islet graft function will be considered for a second islet transplant (intra-hepatic administration) if they do not achieve primary efficacy endpoint criteria at 1 year
| Study group | Role | What they receive |
|---|---|---|
| standard procedure: intrahepatic | Active comparator | Liver infusion: the islet mixture is delivered slowly via injection through a syringe attached to the catheter in the portal vein or portal vein tributary. Access to the portal vein is achieved by percutaneous transhepatic access under fluoroscopic, ultrasonographic, or real-time CT guidance. Alternatively access to a mesenteric or omental venous tributary of the portal vein can be obtained by mini-laparotomy under general anesthesia (transplant site preference or in the extremely rare circumstance that percutaneous access cannot be achieved). At a minimum, portal pressure will be monitored before and after infusion of the islet product. Portal pressure measurements will be documented in the medical record. Gel foam plugs and/or collagen/thrombin paste will be used to embolize the entire peripheral catheter tract immediately before the catheter is withdrawn, to reduce the chances of bleeding. Receives: Biological: Biological: Islet transplantation |
| experimental procedure: omentum | Experimental | Omentum infusion: briefly, islets are spread in the surface of the omentum, in a single omental pouch site. Transplanting in a single site will reduce risks. A single dose of at least 5000 IEQ/KG will be transplanted. The investigators should be able to achieve a meaningful metabolic improvement and prevention of severe hypoglycemia, as previously seen in experience with intraportal islet transplants. Recombinant human thrombin is added to the islets placed on the omentum to promote formation of a gel clot and facilitate adherence to the surface of the omentum. A pouch is then created by folding the omentum. The pouch is secured inn place with stitches. Receives: Biological: Biological: Islet transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
A1c </= 6.5% and no severe hypoglycemia
composite outcome: Proportion of subjects with HbA1c ≤6.5% at 1 year AND free of severe hypoglycemic events from Day 28 to Day 365, inclusive, after the islet transplant.
Measured: 1 year
Secondary outcomes (4)
Insulin requirements
the percent reduction in insulin requirements
Measured: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Insulin secretion
basal (fasting) and 90-min glucose and c-peptide derived from the mixed-meal tolerance test (MMTT)
Measured: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Glucose control
HbA1c
Measured: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
incidence of post-transplant infections, malignancies, morbidity, and other AEs
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2016 (estimated)
- Study startApr 2016
- Primary completionDec 2023
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Islets of Langerhans TransplantationStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lorenzo Piemonti
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Lorenzo Piemonti, Ospedale San Raffaele
- Investigators
- Lorenzo Piemonti, MD, Principal investigator, Ospedale San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02803905
- Sponsor's protocol ID
- ITA OMEN
- Acronym
- ITA-OMEN
- Status last verified
- Feb 2024
- First submitted
- 10 Jun 2016
- Last updated
- 22 Feb 2024
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Monocentric, Open-label, Double-arm, Phase II Trial to Assess the Safety and Efficacy of Allogeneic Islet Cells Transplanted Into the Omentum
- ClinicalTrials.gov ID
- NCT02803905
- Acronym / sponsor ID
- ITA-OMEN / ITA OMEN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Lorenzo PiemontiUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- Dec 2023 (actual)
- Study completion
- Dec 2024 (estimated)
- First posted
- 17 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a phase 2, monocentric, open-label study. The investigators will recruit 12 patients with T1D to be randomly (1:1) assigned to receive islet either into the liver through the portal venous circulation (standard procedure; arm A, n=6) or directly into the omentum (arm B, n=6). Patients will be selected from those eligible for islet Tx based on local practice and guidelines. Immunosuppression will consist of five doses IV infusion of rabbit Anti-thymocyte Globulin (ATG, Thymoglobulin®), starting two days prior to the islet transplant. Maintenance mycophenolate mofetil (MMF) therapy (1-2 g/day as BID dosing) will be started on Day -1 pre-transplant. Tacrolimus will be administered orally twice daily on Day 1 post-transplant to maintain a trough level of 10-12 ng/mL for 3 months, then 6-10 ng/mL thereafter. Etanercept will be given IV before the islet transplant (50 mg), and then at 25 mg (subcutaneously) on POD +3, +7 and +10.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard procedure: intrahepatic | Active comparator | Biological: Biological: Islet transplantationLiver infusion: the islet mixture is delivered slowly via injection through a syringe attached to the catheter in the portal vein or portal vein tributary. Access to the portal vein is achieved by percutaneous transhepatic access under fluoroscopic, ultrasonographic, or real-time CT guidance. Alternatively access to a mesenteric or omental venous tributary of the portal vein can be obtained by mini-laparotomy under general anesthesia (transplant site preference or in the extremely rare circumstance that percutaneous access cannot be achieved). At a minimum, portal pressure will be monitored before and after infusion of the islet product. Portal pressure measurements will be documented in the medical record. Gel foam plugs and/or collagen/thrombin paste will be used to embolize the entire peripheral catheter tract immediately before the catheter is withdrawn, to reduce the chances of bleeding. |
| experimental procedure: omentum | Experimental | Biological: Biological: Islet transplantationOmentum infusion: briefly, islets are spread in the surface of the omentum, in a single omental pouch site. Transplanting in a single site will reduce risks. A single dose of at least 5000 IEQ/KG will be transplanted. The investigators should be able to achieve a meaningful metabolic improvement and prevention of severe hypoglycemia, as previously seen in experience with intraportal islet transplants. Recombinant human thrombin is added to the islets placed on the omentum to promote formation of a gel clot and facilitate adherence to the surface of the omentum. A pouch is then created by folding the omentum. The pouch is secured inn place with stitches. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 <40 years of age, insulin-dependence for > 5 years at the time of enrollment, and a sum of subject age and insulin-dependent diabetes duration of ≥28.
- Absent stimulated c-peptide (<0.3ng/mL) in response to a MMTT
- Involvement in intensive diabetes management
Key exclusion criteria (30 listed)
- Body Mass Index (BMI) >30 kg/m2 or patient weight ≤50 kg.
- Insulin requirement of >1.0 IU/kg/day or <15 U/day.
- HbA1c >10%.
- Untreated proliferative diabetic retinopathy.
- Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.
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 |
|---|---|---|
| Biological: Islet transplantationThis is a single procedure protocol. Only a single islet transplant will be performed in the patient. Islets can be isolated from more than one pancreas donor. The final islet product is a sterile suspension of ≥70% viable, ≥30% pure, allogeneic islets. A minimum of 5000 IEQ/KG will be transplanted. Although this study is a single dose protocol, islet transplant recipients with partial islet graft function will be considered for a second islet transplant (intra-hepatic administration) if they do not achieve primary efficacy endpoint criteria at 1 year | Biological | experimental procedure: omentum, standard procedure: intrahepatic |
Primary outcome
A1c </= 6.5% and no severe hypoglycemia
Time frame: 1 year
composite outcome: Proportion of subjects with HbA1c ≤6.5% at 1 year AND free of severe hypoglycemic events from Day 28 to Day 365, inclusive, after the islet transplant.
4 secondary outcomes
Insulin requirements
Time frame: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Insulin secretion
Time frame: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Glucose control
Time frame: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
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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.
Lorenzo Piemonti, MD principal investigator
Ospedale San Raffaele
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 Biological: Islet transplantation in people with Islets of Langerhans Transplantation and Diabetes Mellitus, Type 1, run by Lorenzo Piemonti at 1 site in Italy.
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 30 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: status not confirmed, as of the sponsor's last update on 22 Feb 2024. 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 Italy. 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?
Results are not available in the source record.
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?
A1c </= 6.5% and no severe hypoglycemia (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2024.