Safety and Feasibility of Novel Therapy for Duodenal Mucosal Regeneration for Type II Diabetes (REGENT-1-US)

• ClinicalTrials.gov Identifier: NCT05014204
• Recruitment Status: Recruiting
• First Posted: August 20, 2021
• Last Update Posted: April 22, 2022
• Sponsor: DyaMX Inc.
• Information provided by (Responsible Party): DyaMX Inc.

Study Description

Brief Summary:

This is a multi-center, open-label study to assess the feasibility and preliminary safety of the Endogenex Device for endoscopic duodenal mucosal regeneration in patients with type 2 Diabetes inadequately controlled on 2-3 non-insulin glucose-lowering medications.

Condition or disease	Intervention/treatment	Phase
Diabetes; Diabetes Type 2; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Disease; Endocrine System Diseases; Diabetes Mellitus	Device: The Endogenex Device	Not Applicable

Detailed Description:

Individuals who sign the informed consent will be screened for study eligibility. Eligible participants will be treated with the Endogenex procedure and followed up for 48 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Feasibility of Endoscopic Application of a Novel Therapy for Duodenal Mucosal Regeneration in the Treatment of Type II Diabetes
• Actual Study Start Date: October 29, 2021
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Interventional; All eligible patients will receive the endoscopic Endogenex procedure.	Device: The Endogenex Device; The Endogenex device is designed to induce duodenal mucosal regeneration using pulsed electric field. The Endogenex procedure is a non-surgical, endoscopic procedure.

Outcome Measures

Primary Outcome Measures :

1. Primary Safety Endpoint [ Time Frame: 12 weeks post-procedure ]
   Portion of participants experiencing device- or procedure-related serious adverse events (SAE)

Secondary Outcome Measures :

1. Changes in HbA1c [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in HbA1c
2. Changes in fasting plasma glucose [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in FPG
3. Changes in insulin resistance [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in HOMA-IR
4. Changes in post-prandial glucose [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes in PPG by mixed meal tolerance test
5. Changes in Weight [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in weight
6. Changes systolic and diastolic blood pressure [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in systolic and diastolic blood pressure
7. Changes in alanine aminotransferase (ALT) [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in ALT
8. Changes in aspartate aminotransferase (AST) [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Mean changes from baseline in AST
9. Changes in glucose-lowering medication usage [ Time Frame: 4, 12, 24, 36, 48 weeks ]
   Changes in usage of glucose-lowering medications

Other Outcome Measures:

1. Procedural success [ Time Frame: At the time of procedure ]
   Percentage of participants with successful DMR procedure
2. Procedural Time [ Time Frame: At the time of procedure ]
   Time between catheter insertion to catheter removal

Eligibility Criteria

• Ages Eligible for Study: 22 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 22- 65 years of age
2. Current diagnosis of T2D
3. History of T2D for at least 3 years and less than or equal to 10 years
4. HbA1C of 7.5-10.0%, inclusive
5. BMI 24-40 kg/m2, inclusive
6. On two to three non-insulin glucose lowering mediations, with one at maximum tolerated dose and another at half-maximum dose at least, with no changes in medication for at least 12 weeks prior to baseline visit prior to baseline visit
7. History of failed attempt to reach glycemic goal by lifestyle modifications
8. Weight stability (defined as a < 5% change in body weight) for at least 12 weeks prior to the screening visit
9. Agree not to donate blood during participation in the study.
10. Able to comply with study requirements and understand and sign the Informed Consent Form
11. Women of childbearing potential must be using an acceptable method of contraception throughout the study
12. Willing and able to use CGM for the duration of the study and comply with study visits and study tasks as required per protocol.
13. Proof of COVID 19 vaccination.

Exclusion Criteria:

1. Diagnosed with type 1 diabetes
2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
3. Probable insulin production failure, defined as overnight fasting C-peptide serum <1 ng/mL (333pmol/l).
4. Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes) in last 2 years.
5. Current use of insulin
6. Hypoglycemia unawareness
7. History of ≥1 severe hypoglycemia episode (defined by needing for third-party assistance) in past 6 months from the screening visit
8. Known autoimmune disease, as evidenced by a positive anti-glutamic acid decarboxylase (GAD) test, including but not limited to celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder. (Participants with adequately controlled primary hypothyroidism may be included).
9. Previous GI surgery that has changed GI anatomy or could limit treatment of the duodenum, such as Billroth 2, Roux-en-Y gastric bypass, gastric band or other similar procedures or conditions.
10. Known history of a structural or functional disorder of the upper GI tract that may impede passage of the device through the upper GI tract or increase risk of tissue damage during an endoscopic procedure, including esophagitis, stricture/stenosis, varices, diverticula, or other disorder of the esophagus, stomach and duodenum.
11. Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen)
12. History of, or gastrointestinal symptoms suggestive of gastroparesis.
13. Acute gastrointestinal illness in the previous 7 days
14. Known history of irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease and Celiac disease
15. History of chronic or acute pancreatitis.
16. Known active hepatitis or active liver disease other than NASH/NAFLD.
17. Alcoholic liver disease, as indicated by ANI > 0
18. Current use of anticoagulation therapy (such as warfarin) that cannot be discontinued for 7 days before and 14 days after the procedure.
19. Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 14 days before and 14 days after the procedure.
20. Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of acetaminophen and low dose aspirin is allowed.
21. Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 12 weeks prior to the baseline visit.
22. Use of drugs known to affect GI motility (e.g. Metoclopramide)
23. Use of weight loss medications such as Meridia, Xenical, Phentermine or over-the-counter weight loss medications (prescription medication)
24. Currently taking, or unable to stop taking dietary supplements or herbal agents, including vitamin C or multivitamins containing vitamin C at >500 mg per day, multivitamins containing biotin (vitamin B7), and supplements for hair, skin, and nail growth. Multivitamins not containing biotin are permitted.
25. Persistent anemia, defined as hemoglobin <10 g/dL.
26. Known history of hemoglobinopathy.
27. Known history of blood donation or transfusion within 3 months prior to the Screening Visit.
28. Known history of cardiac arrythmia
29. 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.
30. Estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73m2 (estimated by MDRD).
31. Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, who have clinically significant leukopenia, who are positive for the human immunodeficiency virus (HIV) or whose immune status makes the participant a poor candidate for clinical trial participation in the opinion of the investigator.
32. History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value outside the normal range at screening)
33. With any implanted electronic devices or duodenal metallic implants
34. Not a candidate for upper GI endoscopy or general anesthesia.
35. Active illicit substance abuse or alcoholism (>2 drinks/day regularly)
36. Active malignancy within the last 5 years (excluding non-melanoma skin cancers)
37. Women breastfeeding
38. Participating in another ongoing clinical trial of an investigational drug or device.
39. Any other mental or physical condition which, in the opinion of the study investigator, makes the participant a poor candidate for clinical trial participation.

40. Critically ill or has a life expectancy <3 years

    Additional exclusion criteria to be confirmed during the screening process:

41. HbA1c < 7.5% or > 10% at baseline visit
42. Any severe hypoglycemic event since the screening visit
43. CGM readings <54 mg/dl in more than 1% of time by CGM since the screening visit
44. CGM readings > 360 mg/dL in more than 1% of time
45. Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic)
46. Women of child-bearing potential with a positive urine pregnancy test at baseline visit
47. LA Grade C or greater esophagitis on endoscopy
48. Abnormalities of the GI tract preventing endoscopic access to the duodenum
49. Anatomic abnormalities in the duodenum that would preclude the completion of the treatment procedure, including tortuous anatomy
50. Endoscopic observation of upper gastrointestinal abnormality such as ulcers, polyps, varices, strictures, congenital or intestinal telangiectasia
51. Any other anatomical or endoscopic abnormalities/characteristics that, in the opinion of the investigator, would preclude safe use of the investigational device or procedure

Contacts and Locations

Contacts

Contact: Marie Steinbrink; 651-329-0351; msteinbrink@endogenex.com

Locations

United States, California

University of Southern California; Recruiting

Los Angeles, California, United States, 90033

Contact: Claudia Riveroll claudia.riveroll@med.usc.edu

Principal Investigator: John Lipham, MD

United States, Minnesota

Cuyuna Regional Medical Center; Not yet recruiting

Crosby, Minnesota, United States, 56441

Contact: Melissa Dyrdal, APRN-CNP melissa.dyrdal@cuyunamed.org

Principal Investigator: Howard McCollister, MD

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Liz Lemke, MPH Lemke.Elizabeth@mayo.edu

Principal Investigator: Andrew Storm, MD

Sponsors and Collaborators

DyaMX Inc.

Investigators

• Study Chair: Daniel DeMarco, MD; Baylor Scott & White

More Information

• Responsible Party: DyaMX Inc.
• ClinicalTrials.gov Identifier: NCT05014204
• Other Study ID Numbers: 346
• First Posted: August 20, 2021
• Last Update Posted: April 22, 2022
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by DyaMX Inc.:

Endoscopy

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases