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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to assess how ultrasound treatment affects blood sugar levels in individuals with type 2 diabetes. Researchers direct ultrasound waves to specific body areas, such as the liver and intestines, for either 30 or 60 minutes. Participants must have managed type 2 diabetes for at least three months with certain oral medications and face challenges in controlling their blood sugar levels. The study does not involve insulin or other advanced diabetes medications. Participants should not have serious complications like heart issues or advanced diabetes-related conditions. As an unphased trial, this study offers a unique opportunity to explore innovative treatment options for managing type 2 diabetes.

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 prior data suggests that this ultrasound treatment is safe for Type 2 Diabetes?

Research has shown that focused ultrasound treatments are generally safe. In a recent study involving 16 people with Type 2 diabetes, ultrasound applied to the liver was well-tolerated, with no serious side effects reported.

Animal studies have also demonstrated that non-invasive ultrasound can help control blood sugar levels. Although more research is needed to fully understand the effects on humans, early findings suggest that ultrasound treatments are safe. Initial studies support this with positive safety results. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for type 2 diabetes, which often involve medications or insulin injections to manage blood sugar levels, this ultrasound approach uses sound waves to stimulate specific areas of the body. Researchers are excited about this method because it targets the liver and intestines directly, potentially improving the body's natural ability to regulate blood sugar without the need for drugs. Additionally, the non-invasive nature of ultrasound makes it a promising alternative for those who want to avoid the side effects associated with traditional diabetes medications.

What evidence suggests that this ultrasound treatment is effective for Type 2 Diabetes?

Research has shown that ultrasound therapy might help control blood sugar levels in people with Type 2 Diabetes. In this trial, participants will receive ultrasound delivery at different durations. For example, one study found that a gentle form of ultrasound, called low-intensity pulsed ultrasound (LIPUS), improved how the body handles sugar and uses insulin, both crucial for managing diabetes. Another study discovered that using ultrasound during treatment significantly lowered blood sugar levels. These findings suggest that ultrasound therapy could be helpful in managing blood sugar levels for people with diabetes. ^{4 6 7 8 9}

Who Is on the Research Team?

Raimund Herzog, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

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 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]

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 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]

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]

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]

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]

Citations

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Ultrasound therapy for exercise-induced muscle soreness and ... The results showed that the women who received ultrasound therapy had significantly less pain and fatigue compared to those who just rested. ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301562925000237

Therapeutic Effects of Different Ultrasound Intensity ... The results indicated that 80mW/cm² intensity level significantly improved glucose tolerance, insulin sensitivity, and metabolic function after LIPUS exposure.

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Ultrasound Stimulation Potentiates Management of ... Discussion. In the single ultrasonic stimulation treatments, there were significant decreases in blood glucose levels during ultrasound stimulation at CV12.

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The Distinct Ultrasound Characteristics and Prognostic ... Studies that examined LH using ultrasound in diabetic patients receiving insulin therapy were included. Two independent reviewers performed ...

5. jofem.org jofem.org/index.php/jofem/article/download/1002/284284724

Evaluation Effect of Low-Intensity Pulsed Ultrasound on ... In this study, we evaluated the effect of low-intensity pulsed ultrasound (LIPUS) on insulin release in type. 2 diabetes (T2D) male rats.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40543424/

Wearable ultrasound regulation of blood glucose levels in ... Results showed that LIPUS-treated db/db mice exhibited a prolonged time for blood glucose to return to baseline levels after 8-week LIPUS ...

7. fusfoundation.org fusfoundation.org/posts/clinical-trial-shows-promising-results-for-focused-ultrasound-neuromodulation-of-diabetes/

Clinical Trial Shows Promising Results for ... Applying focused ultrasound to the liver may improve diabetes symptoms. A recent Phase I clinical trial enrolled 16 participants with Type 2 ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37243693/

a proof of concept, phase 1 trial We report the first safety and feasibility outcomes in subjects with type 2 diabetes (T2D) mellitus and discuss these outcomes in relation to previous pre- ...

9. journals.physiology.org journals.physiology.org/doi/10.1152/ajpendo.00470.2024

Low-frequency ultrasound reverses insulin resistance and ... LFU treatment reversed much of the transcriptomic changes that occurred with insulin resistance and diabetes but had no effect on blood glucose ...