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A Trial to Evaluate Safety, Feasibility and Efficacy of the ReCET Procedure (EMINENT-2) (EMINENT-2)

Primary Purpose

Diabetes Mellitus, Type 2

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
ReCET
Semaglutide, 1.0 mg/mL
Sham procedure
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Type 2 Diabetes, Duodenal ablation, Endoscopy, Electroporation

Eligibility Criteria

28 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosed with type 2 diabetes mellitus 28 - 75 years of age On daily long acting insulin dose ≤ 1 U/kg, with a stable dose (within 10%) over 1 month BMI ≥ 24 and ≤ 42 kg/m2 HbA1c ≤ 64 mmol/mol (8.0%) Fasting C-peptide ≥ 0.2 nmol/L (0.6 ng/ml) Willing to comply with study requirements and able to understand and comply with signed informed consent Exclusion Criteria: Diagnosed with Type 1 Diabetes or with a history of ketoacidosis Current use of multiple daily doses insulin or insulin pump. Current or within the last 3 months use of a GLP-1 analogue. Known autoimmune disease, as evidenced by a positive Anti-GAD test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions History of chronic or acute pancreatitis Known active hepatitis or active liver disease Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) which cannot be discontinued for 3-5 days before and 48 hours after the procedure and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 48 hours before and 48 hours after the procedure in accordance with the local protocol Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 5 days before and 48 hours after the procedure in accordance with the local protocol. Use of aspirin is allowed. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications Anemia, defined as Hgb < 6.2 mmol/l Known history of severe permanent cardiac arrhythmia's with clinical symptoms Significant cardiovascular disease, including known history of valvular disease or myocardial infarction, heart failure, transient ischemic attack, or stroke within 6 months prior to the screening visit With any implanted electronic devices or duodenal metallic implants eGFR or MDRD < 30 ml/min/1.73m^2 Active systemic infection Active malignancy within the last 5 years Not potential candidates for surgery or general anesthesia Active illicit substance abuse or alcoholism Pregnancy or wish getting pregnant in next year Participating in another ongoing clinical trial of an investigational drug or device that can interfere with the current study. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation

Sites / Locations

  • Amsterdam UMCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

ReCET procedure

Sham procedure

Arm Description

Patients receive ReCET (Re-Cellularization via Electroporation Therapy), which is performed using the ReCET device. After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started.

Patients receive sham procedure, this consists of placing an Endogenex catheter, or a catheter with a similar circumference at the endoscopists discretion in the stomach and leaving it in place for 30 minutes. After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started

Outcomes

Primary Outcome Measures

Incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs [safety]
The incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs 24 weeks post ReCET procedure.
Percentage of patients off insulin at 24 weeks [efficacy]
Percentage of patients free of insulin at 24 weeks post ReCET with an HbA1c ≤ 58 mmol/mol compared to sham.

Secondary Outcome Measures

Secondary safety endpoint 1 - hypoglycemic events
Number of hypoglycemic events
Secondary safety endpoint 2 - SAEs
All SAEs
Secondary feasibility endpoint 1 - technical success rate
Technical success rate, defined as percentage of subjects successfully completed the ReCET procedure (defined as ≥ 3 ablations).
Secondary feasibility endpoint 2 - GLP-1RA tolerability
Percentage of subjects adequately using and tolerating GLP-1RA (semaglutide).
Secondary efficay endpoint 1 - HbA1c 48 weeks
Protocol driven number of subjects free of insulin at 48 weeks, including an HbA1c ≤ 58 mmol/mol.

Full Information

First Posted
July 11, 2023
Last Updated
September 18, 2023
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Endogenex
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1. Study Identification

Unique Protocol Identification Number
NCT05984238
Brief Title
A Trial to Evaluate Safety, Feasibility and Efficacy of the ReCET Procedure (EMINENT-2)
Acronym
EMINENT-2
Official Title
Endoscopic Application of Pulsed Electric Fields Using by the Endogenex Generation 2 ReCET System for Duodenal Mucosal Regeneration for EliMination of INsulin in the treatmENT of Type 2 Diabetes: a Randomized Double-blind Sham Controlled Trial to Evaluate Safety, Feasibility and Efficacy Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 3, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Endogenex

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (ReCET system by the Endogenex with the Gen-2 catheter) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus.
Detailed Description
The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (ReCET system by the Endogenex with the Gen-2 catheter) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus and an adequate beta cell reserve in a randomized sham-controlled study. The aimed effect is an adequate or improved glucose regulation without the need for insulin therapy. Secondary effects include improved cardiovascular, hepatic, and metabolic parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Type 2 Diabetes, Duodenal ablation, Endoscopy, Electroporation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
This study is a single-center, double-blind, sham-controlled trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
In this study, both the study team and the study subjects are blinded to the treatment through the 24 week follow-up visit. While the endoscopist is not blinded to individual treatments, he or she is blinded to cohort level data and is not responsible for patient follow-up. At the 24 week visit, the subject and study team are unblinded. The subjects who received the sham treatment undergo ReCET.
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ReCET procedure
Arm Type
Active Comparator
Arm Description
Patients receive ReCET (Re-Cellularization via Electroporation Therapy), which is performed using the ReCET device. After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started.
Arm Title
Sham procedure
Arm Type
Sham Comparator
Arm Description
Patients receive sham procedure, this consists of placing an Endogenex catheter, or a catheter with a similar circumference at the endoscopists discretion in the stomach and leaving it in place for 30 minutes. After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started
Intervention Type
Device
Intervention Name(s)
ReCET
Intervention Description
Investigational product.
Intervention Type
Drug
Intervention Name(s)
Semaglutide, 1.0 mg/mL
Intervention Description
Already registered medicine for type 2 diabetes
Intervention Type
Other
Intervention Name(s)
Sham procedure
Intervention Description
The sham control for the ReCET procedure.
Primary Outcome Measure Information:
Title
Incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs [safety]
Description
The incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs 24 weeks post ReCET procedure.
Time Frame
24 weeks
Title
Percentage of patients off insulin at 24 weeks [efficacy]
Description
Percentage of patients free of insulin at 24 weeks post ReCET with an HbA1c ≤ 58 mmol/mol compared to sham.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Secondary safety endpoint 1 - hypoglycemic events
Description
Number of hypoglycemic events
Time Frame
Through study completion (1 to 1,5 year)
Title
Secondary safety endpoint 2 - SAEs
Description
All SAEs
Time Frame
Through study completion (1 to 1,5 year)
Title
Secondary feasibility endpoint 1 - technical success rate
Description
Technical success rate, defined as percentage of subjects successfully completed the ReCET procedure (defined as ≥ 3 ablations).
Time Frame
24 weeks (after cross-over)
Title
Secondary feasibility endpoint 2 - GLP-1RA tolerability
Description
Percentage of subjects adequately using and tolerating GLP-1RA (semaglutide).
Time Frame
Through study completion (1 to 1,5 year)
Title
Secondary efficay endpoint 1 - HbA1c 48 weeks
Description
Protocol driven number of subjects free of insulin at 48 weeks, including an HbA1c ≤ 58 mmol/mol.
Time Frame
at 48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
28 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosed with type 2 diabetes mellitus 28 - 75 years of age On daily long acting insulin dose ≤ 1 U/kg, with a stable dose (within 10%) over 1 month BMI ≥ 24 and ≤ 42 kg/m2 HbA1c ≤ 64 mmol/mol (8.0%) Fasting C-peptide ≥ 0.2 nmol/L (0.6 ng/ml) Willing to comply with study requirements and able to understand and comply with signed informed consent Exclusion Criteria: Diagnosed with Type 1 Diabetes or with a history of ketoacidosis Current use of multiple daily doses insulin or insulin pump. Current or within the last 3 months use of a GLP-1 analogue. Known autoimmune disease, as evidenced by a positive Anti-GAD test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions History of chronic or acute pancreatitis Known active hepatitis or active liver disease Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) which cannot be discontinued for 3-5 days before and 48 hours after the procedure and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 48 hours before and 48 hours after the procedure in accordance with the local protocol Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 5 days before and 48 hours after the procedure in accordance with the local protocol. Use of aspirin is allowed. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications Anemia, defined as Hgb < 6.2 mmol/l Known history of severe permanent cardiac arrhythmia's with clinical symptoms Significant cardiovascular disease, including known history of valvular disease or myocardial infarction, heart failure, transient ischemic attack, or stroke within 6 months prior to the screening visit With any implanted electronic devices or duodenal metallic implants eGFR or MDRD < 30 ml/min/1.73m^2 Active systemic infection Active malignancy within the last 5 years Not potential candidates for surgery or general anesthesia Active illicit substance abuse or alcoholism Pregnancy or wish getting pregnant in next year Participating in another ongoing clinical trial of an investigational drug or device that can interfere with the current study. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Celine BE Busch, MD
Phone
+31621357593
Email
c.b.busch@amsterdamumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Kim van den Hoek, MD
Phone
+31621357593
Email
k.vandenhoek@amsterdamumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques JG Bergman, MD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam UMC
City
Amsterdam
State/Province
North-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celine BE Busch, MD
Phone
+31621357593
Email
diabetes-onderzoek@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Jacques JG Bergman, MD PhD
First Name & Middle Initial & Last Name & Degree
Celine BE Busch, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://onderzoekdiabetes.nl/
Description
Website for people that are interested in participating.

Learn more about this trial

A Trial to Evaluate Safety, Feasibility and Efficacy of the ReCET Procedure (EMINENT-2)

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