Ultrasound for Type 2 Diabetes

(U/S_in_T2DM Trial)

Overseen By Alice Hahn

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Oral anti-diabetic drugs

Must not be taking: Insulin, DPP-4 inhibitors

Disqualifiers: T1DM, Advanced diabetes complications, Heart disease, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

30 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial requires participants to be on a stable treatment regimen of certain oral anti-diabetic drugs like Metformin, Sulfonylureas, Meglitinides, or Thiazolidinediones. Other medications that interfere with glucose or insulin metabolism are prohibited, so you may need to stop those.

What data supports the effectiveness of the treatment Ultrasound Delivery for Type 2 Diabetes?

There is no direct evidence from the provided research articles supporting the effectiveness of ultrasound delivery for treating Type 2 Diabetes. However, ultrasound is used in managing gestational diabetes by guiding treatment based on fetal growth, which suggests it can play a role in diabetes management. ^{1 2 3 4 5}

Is ultrasound treatment generally safe for humans?

Research on ultrasound treatments, including for diabetes, shows it is generally safe. Studies in animals and some human procedures have not shown significant tissue damage, indicating good safety for potential clinical use. ^{6 7 8 9 10}

How does ultrasound treatment for Type 2 Diabetes differ from other treatments?

Ultrasound treatment for Type 2 Diabetes is unique because it uses sound waves to potentially improve clinical assessments and management of diabetes-related conditions, unlike traditional treatments that often involve medication or lifestyle changes. This approach is novel as it may help in detecting cardiovascular risks and other complications more sensitively than standard clinical examinations. ^{11 12 13 14 15}

What is the purpose of this trial?

This is an open label, exploratory pilot study that will assess the effects of dual site focused pulsed ultrasound treatment on glycemic parameters in subjects with T2DM.

Research Team

Raimund Herzog, MD

Principal Investigator

Yale University

Eligibility Criteria

Adults aged 21-75 with Type 2 Diabetes, BMI of 18 to ≤40 kg/m2, stable on certain oral diabetes meds (like Metformin), and not on insulin or other excluded drugs. They should have an HbA1c level between >7% and <10%, be generally healthy, and women must not be pregnant. Excluded are those with heart disease, severe hypoglycemia history, recent major surgery or infections like COVID-19.

Inclusion Criteria

I am taking diabetes medication like Metformin or similar.

I am not pregnant or breastfeeding and have a negative pregnancy test.

HbA1c > 7.0% and < 10% by local laboratory analysis

Exclusion Criteria

Any nerve stimulation study or implanted stimulator

Participation in an investigational study within 30 days prior to dosing

History of recent traumatic injury

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dual site focused pulsed ultrasound treatment on the liver and intestinal target sites

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Ultrasound Delivery

Trial Overview The trial is testing the impact of focused pulsed ultrasound treatment at two body sites on blood sugar control in people with Type 2 Diabetes Mellitus (T2DM). It's an open label study where all participants know they're receiving the ultrasound treatment.

Participant Groups

Group I: 60 minute, dual site stimulation Experimental Treatment 1 Intervention

Ultrasound Delivery for 60 minutes total: 30 minutes on the liver target site and 30 minutes on the intestinal target site.

Group II: 30 minute, dual site stimulation Experimental Treatment 1 Intervention

Ultrasound Deliveryfor 30 minutes total: 15 minutes on the liver target site and 15 minutes on the intestinal target site.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

GE Healthcare

Industry Sponsor

Trials

307

Recruited

634,000+

Fotis Vlachos

GE Healthcare

Chief Marketing Officer since 2024

PhD in Molecular Biology and Biochemistry from the University of Massachusetts, MBA from the Wharton School of the University of Pennsylvania

Peter J. Arduini

GE Healthcare

Chief Executive Officer since 2022

MBA from Northwestern University, BSc in Marketing from Susquehanna University

Findings from Research

Ultrasound scanning can effectively identify and characterize subcutaneous lipohypertrophy in patients with type 1 diabetes, revealing different tissue types that affect insulin absorption.

In a study of 20 patients, avoiding insulin injections in ultrasound-identified lipohypertrophic areas led to a significant improvement in HbA1c levels after 3 months, highlighting the potential of ultrasound in enhancing glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus. Bertuzzi, F., Meneghini, E., Bruschi, E., et al.[2022]

In a study of 221 women with gestational diabetes mellitus (GDM), ultrasound-guided management led to significantly better neonatal outcomes, including fewer admissions to Special Care or Intensive Care Nursery (29.1% vs. 48.3%) and shorter hospital stays (3.7% vs. 13.8%).

Neonates managed with ultrasound guidance also experienced lower rates of hypoglycemia after birth (42.5% vs. 56.3%), indicating that tailoring GDM management based on fetal growth can enhance safety and health outcomes for newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal ultrasound scans to guide management of gestational diabetes: Improved neonatal outcomes in routine clinical practice. Davidson, SJ., de Jersey, SJ., Britten, FL., et al.[2021]

A flexible ultrasound-based management strategy for gestational diabetes (GDM) led to better pregnancy outcomes, including lower rates of large for gestational age (LGA) and macrosomia, compared to conventional management.

In the study of 229 women, the modified management group had a significantly lower incidence of LGA (7.9% vs 17.9%) and macrosomia (3.3% vs 11.5%), demonstrating that tailoring treatment based on fetal abdominal circumference measurements can optimize care for women with GDM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial. Bonomo, M., Cetin, I., Pisoni, MP., et al.[2020]

In a study of 342 women with type 1 diabetes, ultrasound-based gestational age estimation often resulted in a lower term compared to menstrual-based calculations, indicating a systematic postponement in term estimation.

One in four women with type 1 diabetes had their ultrasound-calculated delivery date postponed by at least one week, which could lead to risks associated with extending pregnancy beyond optimal lengths if solely relying on ultrasound data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discrepancy in term calculation from second trimester ultrasound scan versus last menstrual period in women with type 1 diabetes. Eidem, I., Vangen, S., Henriksen, T., et al.[2019]

In a study of 943 diabetic women with singleton pregnancies, ultrasound scans performed at term were found to be the most accurate for predicting birth weight, with a mean difference of only -30 g from actual birth weight.

The accuracy of ultrasound predictions improved as the gestational age at the time of the scan increased, suggesting that fetal growth assessments closer to delivery are crucial for effective delivery planning in diabetic pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Timing of Prenatal Ultrasound in Predicting Birth Weight in Diabetic Pregnancies. Nash, CM., Woolcott, C., O'Connell, C., et al.[2021]

In a pre-clinical study using mice, low-frequency, low-intensity therapeutic ultrasound significantly increased insulin levels by approximately 50 pM immediately after treatment, while sham-treated animals showed a decrease in insulin levels.

The ultrasound treatment did not cause any visible damage to pancreatic tissue, suggesting it is a safe method for inducing insulin release, marking a promising step towards potential treatments for early-stage type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Ultrasound-Induced Insulin Release in Vivo. Singh, T., Suarez Castellanos, I., Bhowmick, DC., et al.[2021]

Ultrasound-targeted microbubble destruction (UTMD) effectively delivered GLP-1 gene therapy in macaques with type 2 diabetes, enhancing cell membrane penetration and increasing GLP-1 expression.

The treatment led to significant improvements in pancreatic beta cell regeneration and better regulation of plasma glucose levels over a 6-month monitoring period, indicating its potential as a safe and effective alternative for T2D management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation. Zhang, C., Chen, S., Li, Q., et al.[2021]

The study of 22 recipients undergoing human islet transplantation (IT) demonstrated that ultrasound (US) guidance throughout the procedure resulted in a 100% technical success rate with minimal complications, including manageable abdominal bleeding in 17.1% of cases.

Primary graft function was optimal in 36.4% of patients, indicating that US-guided IT is an effective method for treating diabetes, with complications being either self-limiting or treatable with noninvasive techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Human Islet Transplantation: Safety, Feasibility, and Efficacy Analysis. Yang, D., Zhuang, B., Duan, J., et al.[2023]

Therapeutic ultrasound (TUS) at a frequency of 1 MHz can effectively deliver acoustic pressures to the pancreas, which have been shown to induce insulin release in preclinical studies, suggesting potential efficacy for treating type 2 diabetes mellitus (T2DM).

Simulation studies using 2D models of human abdomens indicate that applying ultrasound directly from the front of the abdomen at 5 W/cm2 is a feasible method for non-invasive treatment of T2DM in a clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling of Ultrasound Stimulation of Adolescent Pancreas for Insulin Release Therapy. Saab, G., Singh, T., Chen, AW., et al.[2023]

Ultrasound-mediated gene delivery (UMGD) was successfully used to transfer genes into pig livers through a minimally invasive method, showing significant gene transfer with over 100-fold increase in luciferase activity compared to untreated areas.

The technique demonstrated minimal tissue damage while achieving effective gene delivery, indicating its potential for clinical applications in treating genetic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Ultrasound-Mediated Nonviral Gene Delivery to the Liver in a Porcine Model. Tran, DM., Zhang, F., Morrison, KP., et al.[2021]

In a study of 43 pregnancies complicated by insulin-dependent diabetes, level II ultrasound identified 4 out of 10 congenital anomalies, demonstrating a sensitivity of 67% and a specificity of 100%.

The prenatal diagnosis of congenital anomalies through ultrasound influenced management decisions in 3 out of the 4 cases, highlighting the potential of high-resolution ultrasound as a valuable screening tool for these pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of ultrasound diagnosis of fetal anomalies in women with pregestational diabetes: University of Florida experience. Gomez, KJ., Dowdy, K., Allen, G., et al.[2019]

In a study of 142 diabetic pregnancies, abdominal circumference (AC) was the most reliable ultrasound measurement for predicting macrosomia, with a 71% accuracy rate, followed by transverse abdominal diameter (TAD) at 60%.

The study suggests that ultrasound can effectively assess fetal growth and placental maturity, which may help in planning delivery for at-risk pregnancies, although further research is needed to clarify the relationship between placental maturity and fetal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between ultrasound findings in pregnancy and neonatal morbidity. Pachi, A., Fallucca, F., Gerlini, GF., et al.[2019]

Ultrasound examinations in pregnancies affected by maternal hyperglycemia are crucial for early detection of congenital malformations and assessing fetal well-being, which can significantly impact clinical decisions regarding delivery.

The review highlights the importance of ultrasound in managing pregnancies complicated by diabetes mellitus, emphasizing its role in monitoring fetal growth and guiding healthcare providers in determining the optimal timing and method of delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fetus of a diabetic mother: sonographic evaluation. Nizard, J., Ville, Y.[2016]

Ultrasound can enhance the assessment of cardiovascular risk in diabetology by evaluating carotid arteries for plaques and measuring intima media thickness.

It is effective in detecting liver steatosis and identifying lipohypertrophy, which can lead to glycemic fluctuations and increased hypoglycemia risk, making it a valuable tool for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point-of-Care Ultrasound (POCUS) in the Field of Diabetology. Vandemergel, X.[2021]

In a study of 172 diabetic women requiring insulin, using abdominal circumference (AC) and femur length (FL) to estimate fetal weight was found to be as accurate as more complex models, with a mean absolute error of 86 g/kg.

The study indicated that ultrasound estimation of fetal weight has limitations in detecting macrosomia, as the accuracy of predicting whether a newborn would be macrosomic (≥4 kg) was not significantly improved with additional measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimators of birth weight in pregnant women requiring insulin: a comparison of seven sonographic models. McLaren, RA., Puckett, JL., Chauhan, SP.[2016]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Fetal ultrasound scans to guide management of gestational diabetes: Improved neonatal outcomes in routine clinical practice. [2021]

3. France pubmed.ncbi.nlm.nih.gov

Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Discrepancy in term calculation from second trimester ultrasound scan versus last menstrual period in women with type 1 diabetes. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Optimal Timing of Prenatal Ultrasound in Predicting Birth Weight in Diabetic Pregnancies. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Therapeutic Ultrasound-Induced Insulin Release in Vivo. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Human Islet Transplantation: Safety, Feasibility, and Efficacy Analysis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Modeling of Ultrasound Stimulation of Adolescent Pancreas for Insulin Release Therapy. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Ultrasound-Mediated Nonviral Gene Delivery to the Liver in a Porcine Model. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Evaluation of ultrasound diagnosis of fetal anomalies in women with pregestational diabetes: University of Florida experience. [2019]

12. Denmark pubmed.ncbi.nlm.nih.gov

Relationship between ultrasound findings in pregnancy and neonatal morbidity. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

The fetus of a diabetic mother: sonographic evaluation. [2016]

14. Egypt pubmed.ncbi.nlm.nih.gov

Point-of-Care Ultrasound (POCUS) in the Field of Diabetology. [2021]

15. United States pubmed.ncbi.nlm.nih.gov

Estimators of birth weight in pregnant women requiring insulin: a comparison of seven sonographic models. [2016]