Transcutaneous Electrical Nerve Stimulator to Improve Blood Glucose Control in Patients With Type 2 Diabetes Mellitus

A Prospective, Double Blind, Randomized, Placebo- Controlled Trial of Transcutaneous Electrical Nerve Stimulator (DW1330) to Improve Blood Glucose Control in Patients With Type 2 Diabetes

The primary study objective is to demonstrate the use of "Dragon Waves Resonant Home Care" Electronic Nerve Stimulator (DW1330) is associated with improvement of blood glucose control, as measured by change of glycated hemoglobin (HbA1c). The second study objectives are to demonstrate that DW1330 is associated with the mechanism of glycemic control and inflammation pathways. The study is also aimed to investigate the safety of DW1330.

This is a multi-center, prospective, double blind, randomized, placebo-controlled trial of transcutaneous electrical nerve stimulator (DW1330) to improve blood glucose control in patients with type 2 diabetes. Subjects with type 2 diabetes who meet inclusion/exclusion criteria will be randomized to either of the 2 groups below:

1. DW1330
2. Placebo (sham TENS delivering ineffective pulse wave)

After enrollment, subjects will be randomly assigned to receive one of the study treatments in a double-blind fashion. All patients enrolled should perform 1 treatment within 1 hour after dinner 5 days a week. The end of a 20 week treatment period, subjects will be followed for an additional 2 weeks for safety follow-up. The time frame includes 2 weeks of screening, 20 weeks of treatment, and 2 weeks of post-treatment follow-up.

Study visits will occur every 2 or 4 weeks depending on the study phase. At randomization visit study device will be dispensed at the site, during the treatment period visits, all Adverse Events (AEs) as well as follow-up for all AEs that have not been resolved will be recorded, changes to concomitant medications will be noted, vital signs will be taken, and efficacy evaluations will be performed as well. Investigators, site staff, subjects, and the study team will be blinded to the device assigned. The study includes collection of blood and urine samples. The end-of-treatment visit and the last estimation of glycemic control will occur at week 20 (visit 8) for all subjects. In addition, 2-week follow up will occur in order to collect safety data after the device is returned. The final visit will be at week 22 (visit 9). Subjects will be encouraged to complete all planned visits regardless of their adherence to study device administration.

Inclusion Criteria:

1. Male and female subjects age 30 through 80 years;
2. Type 2 diabetes mellitus (T2DM) patients on stable oral anti-diabetic drugs for more than 3 months, and can maintain stable during study maintenance period;
3. HbA1c between 7.5 and 10% inclusive;
4. Subjects who are able and willing to perform self-monitoring of plasma glucose and self-administration of study device for the entire trial period;
5. Subjects who are able and willing to keep a diary;
6. Able and willing to sign informed consent and return for follow-up assessments.

Exclusion Criteria:

1. Subject has had any of the following new diagnoses within 1 year of screening:

   myocardial infarction, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure(NYHA III-IV), ventricular rhythm disturbances or thromboembolic disease;

2. Subjects with prior pancreatitis;

3. Subjects with insulin therapy (except for short term uses no longer than 7 days) or injectable antihyperglycemic agents (AHAs) within 3 months;

4. Female with a positive pregnancy test, planning to become pregnant during screening, active treatment, or the follow up period, breastfeeding, or judged to be using inadequate contraceptive methods;

5. Subjects who underwent previous intra abdominal, GI tract surgery or a major abdominal trauma within 6 months prior to screening visit;

6. Subjects with other implanted electrical stimulation devices;

7. Subject has any unresolved adverse skin condition in the area of device placement;

8. ALT/AST greater than 3 x upper limit of the institution's normal range (ULN) and/or total bilirubin ≥ 2.0 x ULN, active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, hepatic cirrhosis, primary biliary cirrhosis, or active symptomatic gallbladder disease;

9. Subjects with moderate or severe renal impairment (serum creatinine ≥1.5 mg/dL in males or ≥ 1.4 mg/dL in females or urine microalbumin-creatinine ratio (ACR) >300 mg/g), conditions of congenital renal glucosuria, unstable or rapid progressing renal disease;

10. Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia, coagulopathy);

11. Subjects with acute metabolic complications (such as ketoacidosis, lactic acidosis or hyperosmolar), proliferative diabetic retinopathy or macular edema within 6 months before screening;

12. Subjects with a history of malignancy ≤5 years prior to screening, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer;

13. Subjects a history of alcohol or drug abuse within 1 year prior to screening;

14. Subjects who received another investigational agent within 30 days prior to screening;

15. Subjects who are unlikely to be available for follow-up as specified in the protocol;

16. Subjects with a past or present psychiatric condition that may impair his or her ability to comply with the study procedures;

17. Subjects with conditions that, in the judgment of the investigator, precludes successful participation to the study;

18. Subjects with fever(body temperature> 37.5°C), perceptual function lost, or any metal implants.