A U.S. Pilot Human Investigation of RadiofrEquency Vapor Ablation System to Evaluate Safety, TOleRability, and Effectiveness for Proximal Intestinal Mucosal Ablation in Patients With Type 2 Diabetes Mellitus (RESTORE-1 Study) (RESTORE-1)

The purpose of this study is to assess the safety, tolerability and effectiveness of RF vapor ablation of the proximal intestinal mucosa. This study will test the hypothesis that RF vapor ablation will result in improvement in glycemic parameters, without Serious Adverse Events (SAE) or Unanticipated Adverse Device Effects (UADE).

Study Overview

• Status: Recruiting
• Conditions: Type-2 Diabetes Mellitus
• Intervention / Treatment: Device: RF Vapor Ablation

Detailed Description

The main aims of the study are :

Evaluate the safety of the device and procedure based on the reported adverse events that occur.

Evaluate device tolerability based on pain scores reported by patients. Evaluate the effectiveness of the device and procedure by comparing change in HbA1c from baseline to 168 days post procedure.

The subject population for this study are adults (22-65 years of age) with type-2 diabetes mellitus. Study participation is 6 months for each patient.

The study is comprised of 5 phases: Screening, Run-in, Pre-procedure tests, RF Vapor ablation procedure, and Post-vapor ablation follow-up (up to 168 days).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Krithika Rupnarayan, MD, MPH; Phone Number: 925-223-6392; Email: krupnarayan@aquaendoscopy.com
• Study Contact Backup: Name: Alina Stoica; Email: astoica@aquaendoscopy.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Honorhealth Research Institute
      • Principal Investigator: James Swain, MD
      • Contact: Heather Lane, M. Ed.; Phone Number: 480-583-7406; Email: hlane@honorhealth.com
    • Scottsdale, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic
      • Contact: Suraj Phull; Phone Number: 4805745993; Email: Phull.Suraj@mayo.edu
      • Principal Investigator: Rahul Pannala, MD
  • California
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
      • Contact: Brittany Dennis; Phone Number: 949-764-6896; Email: Brittany.Dennis@hoag.org
      • Principal Investigator: Jennifer Phan, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina School of Medicine
      • Principal Investigator: Nicholas J Shaheen, MD, MPH
      • Contact: Nicholas Susan E Moist, CCRP; Phone Number: 919-918-5900; Email: susan_moist@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and non-pregnant women 22-65 years of age
2. Diagnosed with T2DM for at least 1 year and less than or equal to 15 years
3. HbA1C of 7.5 - 10% (58-86 mmol/mol)
4. BMI ≥ 24 and ≤ 40 kg/m2

5. On one or more non-insulin glucose-lowering medications, with no therapeutic changes in medication regimen for at least 12 weeks prior to the screening visit, to ensure stable glycemic control.

   Note 1: Exception for sulfonylureas (SU): For safety reasons, subjects taking sulfonylureas (limited to glipizide or glimepiride only) will be required to undergo a protocol-mandated reduction to ≤50% of the maximum labeled dose during the run-in phase. This adjustment is intended solely to minimize the risk of hypoglycemia during intensive monitoring and dietary standardization and will not be considered a therapeutic change for purposes of eligibility. Subjects unwilling to comply with this dose reduction will be excluded.

   Note 2: GLP-1s are considered non-insulin glucose lowering medications.

6. Agrees to use an additional glucose-lowering treatment (e.g., liraglutide, other OAD except for glyburide), if recommended by the study Investigator in case of persistent hyperglycemia.
7. Weight stability (defined as a < 5% change in body weight) in the 12 weeks prior to the screening visit. Participants should agree to refrain from using over the counter or herbal supplements intended for weight loss. Participants already on a prescribed weight loss drug should agree to not further titrate their medications during the study.
8. Women of childbearing potential must be using at least one acceptable method of contraception throughout the study
9. Willing and able to use CGM for the duration of the study and comply with study visits and study tasks as required per protocol.
10. Able to comply with study requirements and understand and sign the Informed Consent Form

Exclusion Criteria:

1. Diagnosis of Type-1 Diabetes
2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
3. Probable insulin production failure, defined as serum C-peptide of 0.3-0.6 nmol/l.
4. Current or previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes) in the last 2 years.
5. Hypoglycemia unawareness as defined by a score of 4 or higher on a Gold score questionnaire suggestive of impaired awareness of hypoglycemia (IAH).
6. History of severe hypoglycemia (2 or more severe hypoglycemic event, as defined by need for third-party assistance, in the last 6 months from the screening visit).
7. Subjects with untreated or unstable microvascular complications of diabetes such as retinopathy, nephropathy, and neuropathy. Subjects who have been appropriately treated/monitored and stable for the prior 3 months before study participation can be included as determined as safe and reasonable by the study PI.
8. Known systemic autoimmune disease that is uncontrolled or requiring steroids or biologics, including a positive anti-glutamic acid decarboxylase (GAD) test. Systemic autoimmune diseases include but not limited to celiac disease, duodenal Crohn disease or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other systemic autoimmune connective tissue disorder. (Participants with adequately controlled primary hypothyroidism or with mild to moderate psoriasis managed with topical therapy-affecting less than 10% of body surface area and not involving special areas (e.g., face, palms)-may be included).
9. Previous GI surgery that could limit access to the duodenum such as Billroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions. (Patients who have undergone a laparoscopic sleeve gastrectomy (LSG) or an endoscopic sleeve gastrectomy (ESG) procedure more than one year prior to enrollment will not be excluded from participation in this study.)
10. History of chronic pancreatitis or a diagnosis of idiopathic acute pancreatitis within the past 12 months.
11. Documented history of diabetic gastroparesis confirmed by gastric emptying study.
12. Known active hepatitis or liver disease, excluding nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD).
13. Symptomatic gallstones, or acute gastrointestinal illness in the previous 7 days.
14. Known history of severe irritable bowel syndrome, radiation enteritis or other inflammatory bowel syndrome, such as Crohn's disease and Celiac disease.
15. Alcoholic liver disease, as indicated by ANI>-0.66 and AUDIT-C questionnaire
16. Known history of a structural or functional esophageal disorder that could impede endoscope passage or elevate the risk of esophageal injury during an endoscopic procedure, including but not limited to moderate-severe (Los Angeles Grade C or D) esophagitis, dysphagia due to achalasia or stricture/stenosis, esophageal varices greater than Grade 2, history of esophageal perforation, or any other clinically significant esophageal condition.
17. Presence of upper gastrointestinal conditions, including active ulcers, varices, strictures, congenital or acquired proximal intestinal telangiectasia, active H. pylori infection.
18. Current use of anticoagulation therapy (vitamin K antagonists, such as warfarin, or current use of direct-action oral anticoagulants (DOACs) that cannot be safely discontinued peri procedurally
19. Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 7 days before and 7 days after the procedure.
20. Unable to discontinue high-dose non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of acetaminophen and low dose aspirin, PRN over the counter NSAIDs 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. Persistent anemia, defined as hemoglobin <10 g/dl on two consecutive measurements >6 weeks apart.
23. Known history of hemoglobinopathy.
24. Known history of blood donation or transfusion within 3 months prior or screening or anticipated blood donation during the study period.
25. Significant cardiovascular disease, including known history of valvular heart disease, or myocardial infarction, heart failure, transient ischemic attack, or stroke within 12 months prior to the Screening Visit.
26. Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic).
27. Estimated glomerular filtration rate (eGFR) ≤ 45 ml/min/1.73m2 (estimated by MDRD).
28. Known immunocompromised status, including but not limited to: individuals who have undergone organ transplantation, receipt of chemotherapy, or radiotherapy within the past 12 months, clinically significant leukopenia, confirmed human immunodeficiency virus (HIV) infection, or any other condition impacting immune function that, in the opinion of the investigator, renders the participant unsuitable for trial participation.
29. History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value >1.5x of the upper limit of normal range at screening)
30. In the opinion of the Investigator, the participant is not an appropriate candidate for upper GI endoscopy or general anesthesia.
31. Active illicit substance abuse or Alcohol Use Disorder (AUD) (consuming more than 14 drinks per week for men or more than seven drinks per week for women)
32. Active malignancy within the last 5 years (excluding non-melanoma skin cancers)
33. Women who are currently breastfeeding
34. Participating in another ongoing clinical trial of an investigational drug or device.
35. Any other physical or mental condition that, in the opinion of the investigator, would make the participant an unsuitable candidate for clinical trial participation.
36. Critically ill or has a life expectancy <3 years.
37. Use of a cardiac pacemaker, implantable cardioverter-defibrillator (AICD), duodenal metallic implants, or any other implanted electronic medical devices.
38. General contraindications to deep or conscious sedation, general anesthesia, or upper gastrointestinal (GI) endoscopy, including individuals deemed high-risk by an anesthesiologist (e.g., ASA Physical Status Classification of IV or higher).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study arm- RF Vapor Ablation arm (PIMA arm); This is a single arm study. All enrolled patients will be included in this arm	Device: RF Vapor Ablation; RF Vapor ablation of the proximal intestinal mucosa; Other Names: Aqua Medical RF Vapor System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoint	Number of subjects with reported device or procedure related SAEs or UADEs.	6 months
Tolerability endpoint	Descriptive statistics on Visual Analogue Scale(VAS) pain scores (A Visual Analog Scale (VAS) pain score is a patient's self-reported measure of pain intensity, marked on a straight line scale from 0-10, with "no pain" at the zero-end and "worst imaginable pain" at 10.)	14 days
Efficacy endpoint	Change in HbA1c from baseline to 6 months post procedure	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c at 3 months post procedure	Change in HbA1c (from baseline) at 3 months post procedure will be analyzed	3 months
Change in FPG from baseline to 3 months and 6 months post procedure	Change in Fasting Plasma Glucose from baseline to 3 months and 6 months post procedure	6 months
Proportion of ablation-treated subjects with an HbA1c improvement > 0.5% from baseline at 6 months.	Proportion of ablation-treated subjects with an HbA1c improvement > 0.5% from baseline at 6 months.	6 months
Change in HOMA-IR from baseline to 6 months post procedure.	Change in HOMA-IR from baseline to 6 months post procedure.	6 months
Change in UACR from baseline to 6 months post procedure.	Change in Urine Albumin-Creatinine Ratio from baseline to 6 months post procedure.	6 months
Change in ALT and AST from baseline to 6 months post procedure.	Change in ALT and AST from baseline to 6 months post procedure.	6 months

Collaborators and Investigators

• Sponsor: Aqua Medical, Inc.
• Investigators: Principal Investigator: Nicholas Shaheen, MD, University of North Carolina

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; T2DM; RESTORE-1; Type-2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus
• Other Study ID Numbers: CLD-1021-US

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes