Diabetes, Diabetes Mellitus, Diabetes Mellitus, Type 2, Diabetes Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Disease
Conditions
Keywords
Endoscopy, type 2 diabetes
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.
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.
Interventions
DEVICEThe 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.
Sponsors
Endogenex, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Experiencing Device- or Procedure-Related Serious Adverse Events (SAE) | 12 weeks post-procedure | Number of participants experiencing device- or procedure-related serious adverse events (SAE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean HbA1c by Follow-up Visit | at 4,12, 24, and 48 Weeks Post Procedure | Mean HbA1c by Post Procedure Follow-up Visits |
| Mean Fasting Plasma Glucose (FPG) by Visit | Follow-up at 4,12, 24, 36, and 48 weeks post procedure | Mean Fasting Plasma Glucose (FPG) at Post Procedure Follow-up Visit |
| Mean Weight by Follow-up Visit | Follow-up at 4,12, 24, 36, and 48 weeks post procedure | Mean weight by Post Procedure Follow-up Visit |
Other
| Measure | Time frame | Description |
|---|---|---|
| Procedural Success | At the time of procedure | Percentage of participants with successful DMR procedure |
| Procedural Time | At the time of procedure | Time between catheter insertion to catheter removal |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 3 study sites in the US. Twenty participants were enrolled (i.e. received Endogenex treatment). Two participants did not complete the study due to patient withdrawal and physician withdrawal to relocation.
Pre-assignment details
Pre-assignment did not occur in this study. All participants that met inclusion criteria and none of the exclusion criteria received treatment with the Endogenex device. At the time of the procedure, a screening endoscopy was performed on all participants to visually confirm the suitability of GI anatomy and excluding any participants with anatomy that met exclusion or preclude operator's ability to safely complete the treatment.
Participants by arm
| Arm | Count |
|---|---|
| Interventional Arm- Endogenex (PEF) Treatment Participants meeting inclusion and not meeting exclusion were treated with the Endogenex device. The Endogenex device is designed to induce duodenal mucosal regeneration using pulsed electric field via non-surgical, endoscopic approach. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Interventional Arm- Endogenex (PEF) Treatment |
|---|---|
| Age, Customized Age | 54.4 years STANDARD_DEVIATION 7.8 |
| BMI (kg/m²) | 32.4 kg/m² STANDARD_DEVIATION 4.3 |
| Duration of Diabetes (years) | 6.7 years STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HbA1c (%) | 8.3 % STANDARD_DEVIATION 0.54 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
| Weight (lbs) | 224 lbs STANDARD_DEVIATION 39 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 5 / 20 |
Outcome results
Primary
Participants Experiencing Device- or Procedure-Related Serious Adverse Events (SAE)
Number of participants experiencing device- or procedure-related serious adverse events (SAE)
Time frame: 12 weeks post-procedure
Population: Primary endpoint was performed at 12 weeks. At the 12 weeks, data from all 20 participants were available. Two participants exited the study at the 24 week visit, resulting in the 18 participants completing the study at 48 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interventional Arm- Endogenex (PEF) Treatment | Participants Experiencing Device- or Procedure-Related Serious Adverse Events (SAE) | 0 Number of Participants with related SAE |
Secondary
Mean Fasting Plasma Glucose (FPG) by Visit
Mean Fasting Plasma Glucose (FPG) at Post Procedure Follow-up Visit
Time frame: Follow-up at 4,12, 24, 36, and 48 weeks post procedure
Population: Two participants were exited from the study by 24 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interventional Arm- Endogenex (PEF) Treatment | Mean Fasting Plasma Glucose (FPG) by Visit | Mean FPG at Week 4 post procedure | 140.1 mg/dL | Standard Deviation 28.6 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Fasting Plasma Glucose (FPG) by Visit | Mean FPG at Week 12 post procedure | 155.7 mg/dL | Standard Deviation 28.8 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Fasting Plasma Glucose (FPG) by Visit | Mean FPG at Week 24 post procedure | 155.9 mg/dL | Standard Deviation 42.7 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Fasting Plasma Glucose (FPG) by Visit | Mean FPG at Week 36 post procedure | 150.8 mg/dL | Standard Deviation 24.2 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Fasting Plasma Glucose (FPG) by Visit | Mean FPG at Week 48 at post procedure | 161.6 mg/dL | Standard Deviation 37 |
Secondary
Mean HbA1c by Follow-up Visit
Mean HbA1c by Post Procedure Follow-up Visits
Time frame: at 4,12, 24, and 48 Weeks Post Procedure
Population: Two participants were exited from the study by 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interventional Arm- Endogenex (PEF) Treatment | Mean HbA1c by Follow-up Visit | Mean HbA1c at Week 4 Post Procedure | 7.2 HbA1c % | Standard Deviation 0.7 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean HbA1c by Follow-up Visit | Mean HbA1c at Week 12 Post Procedure | 6.7 HbA1c % | Standard Deviation 0.7 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean HbA1c by Follow-up Visit | Mean HbA1c at Week 24 Post Procedure | 6.9 HbA1c % | Standard Deviation 1.1 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean HbA1c by Follow-up Visit | Mean HbA1c at Week 36 Post Procedure | 7.0 HbA1c % | Standard Deviation 0.7 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean HbA1c by Follow-up Visit | Mean HbA1c at Week 48 Post Procedure | 7.2 HbA1c % | Standard Deviation 0.8 |
Secondary
Mean Weight by Follow-up Visit
Mean weight by Post Procedure Follow-up Visit
Time frame: Follow-up at 4,12, 24, 36, and 48 weeks post procedure
Population: Two participants were exited by 24 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interventional Arm- Endogenex (PEF) Treatment | Mean Weight by Follow-up Visit | Mean Weight at Week 4 Post Procedure | 215.6 lbs | Standard Deviation 38.1 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Weight by Follow-up Visit | Mean Weight at Week 12 Post Procedure | 209.3 lbs | Standard Deviation 36.1 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Weight by Follow-up Visit | Mean Weight at Week 24 Post Procedure | 214.9 lbs | Standard Deviation 40.3 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Weight by Follow-up Visit | Mean Weight at Week 36 Post Procedure | 213.3 lbs | Standard Deviation 41.1 |
| Interventional Arm- Endogenex (PEF) Treatment | Mean Weight by Follow-up Visit | Mean Weight at Week 48 Post Procedure | 217.8 lbs | Standard Deviation 41.7 |
Other Pre-specified
Procedural Success
Percentage of participants with successful DMR procedure
Time frame: At the time of procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Interventional Arm- Endogenex (PEF) Treatment | Procedural Success | 20 Participants |
Other Pre-specified
Procedural Time
Time between catheter insertion to catheter removal
Time frame: At the time of procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interventional Arm- Endogenex (PEF) Treatment | Procedural Time | 82.9 minutes | Standard Deviation 20.1 |