Pancreas Ultrasound Imaging in type1 Diabetes

Contrast Enhanced Ultrasound Imaging of Pancreas Blood Flow in type1 Diabetes

The overall goal of this study is to develop and test a novel method involving ultrasound imaging, in order to detect the development of type 1 diabetes. In this study the investigators will first establish a standard operating procedure for measuring pancreas blood flow speed and volume in the pancreas of human subjects. The investigators will then determine 1) whether these pancreas blood flow factors differ between healthy subjects and those who have recently developed type1 diabetes; and 2) how variable measurements are in healthy subjects and subjects that recently developed type1 diabetes, both between subjects and over time. To address these aims the investigators will perform pancreas ultrasound measurements in each subject using an approved injectable 'bubble' contrast agent that allows measurement of pancreas blood flow. The investigators will compare ultrasound measurement with characteristics of the subject's type 1 diabetes, including genetic factors, glucose levels and other circulating factors, as well as other factors that may influence blood flow in the pancreas independent of type1 diabetes. The successful conclusion of this study will indicate whether measuring pancreas blood flow speed/volume will be helpful in monitoring whether type1 diabetes will emerge and thus will allow a large scale study to answer this question.

Study Overview

• Status: Recruiting
• Conditions: Type1diabetes; Pancreas Inflamed; Insulitis
• Intervention / Treatment: Drug: Definity Suspension for Injection

Detailed Description

Study Design and Research Methods

Part I:

5 subjects from SOP group Goal: Optimize settings for destruction-replenishment contrast-enhanced ultrasound scan

1. Subject recruited at the Barbara Davis Center
2. Subject provides written consent
3. Review medical history (exclusion if required)
4. Subject refrains from eating for ~6h prior to measurement
5. Subject visits University of Colorado Hospital CTRC echo lab
6. CTRC staff places peripheral intravenous line (PIV)
7. Research staff collects vital signs, height and weight
8. Subject received conventional ultrasound scan to locate pancreas tail (by Sonographer, verified by radiologist).
9. Subject receives DEFINITY dose
10. Subject receives destruction-replenishment contrast-enhanced ultrasound scan (adjust settings to optimize)
11. Pause for 30 minutes, allowing subject to stand and move
12. Repeat steps 9-11 (once).
13. Subject de-identified.
14. Analyze data.

Part II:

30 subjects from control group (healthy controls and multiple islet autoantibody positive subjects), 15 subjects from T1D group.

Goal: characterize subject variability and test whether healthy subjects and those with T1D show differing contrast measures

1. Subject recruited at the Barbara Davis Center
2. Subject provides written consent
3. Review medical history (exclusion if required)
4. Subject refrains from eating for ~6h prior to study
5. Subject visits University of Colorado Hospital CTRC echo lab
6. Subject completes questionnaire (family history of diabetes, exclusion criteria)
7. CTRC staff places peripheral intravenous line (PIV)
8. Research staff collects vital signs, height and weight
9. Subject received conventional ultrasound scan to locate pancreas tail (by Sonographer, verified by radiologist).
10. Subject receives DEFINITY dose
11. Subject receives destruction-replenishment contrast-enhanced ultrasound scan (under SOP)
12. Pause for 30 minutes, allowing subject to stand and move
13. Repeat steps 10-12 (once).
14. Subject de-identified
15. Analyze data.

In part I a single repeat measurement may be made to aide in the optimization of data collection. In part II a single repeat measurement is made to assess short-term intra-subject measurement variability.

In part I and part II, a subject will be asked to return on a separate date (within 1 year of the initial scan) for a repeat procedure using an additional DEFINITY delivery method (bolus or infusion, whichever was not given at the initial visit) or if data collection was not of sufficient quality during the first visit.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Morgan Sooy; Phone Number: 303 724 7526; Email: morgan.sooy@cuanschutz.edu
• Study Contact Backup: Name: Hali Broncucia; Phone Number: 303 724 7526; Email: hali.broncucia@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz, Barbara Davis Center
      • Contact: Hali C Broncucia, MA; Phone Number: 303-724-7526; Email: hali.broncucia@cuanschutz.edu
      • Contact: Morgan Sooy, MS; Phone Number: 303-724-5686; Email: morgan.sooy@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Group 1 subjects will be healthy subjects who will receive contrast-enhanced ultrasound 'destruction-replenishment' measurements, in order to optimize and establish the standard operating procedure (SOP) for this measurement in the pancreas of human subjects. This SOP will then be applied to Group 2 (healthy subjects and autoantibody positive subjects) and Group 3 (recent onset type1 diabetes) subjects as part of the cross-sectional study. Classification of type 1 diabetes includes meeting ADA criteria for diabetes, within 180 days of diagnosis, and evidence of at least 1 islet-associated autoantibody.

Description

Inclusion Criteria:

• Male or non-pregnant female age 18-65
• Ability and willingness of patient to participate fully in all aspects of this clinical study
• Written informed consent obtained and documented

Exclusion Criteria:

• Excessive body size preventing effective scan of the pancreas as determined by sonographer
• Evidence of exocrine pancreatic disease, including pancreatitis, cystic fibrosis, pancreatic adenocarcinoma, or neuroendocrine tumor.
• Subjects who are pregnant or breast-feeding
• Subjects incapable of giving assent/informed written consent
• Known or suspected hypersensitivity to perflutren
• Known history or suspected unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, or serious ventricular arrhythmias)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 3; T1D subjects. Part II of study (cross-sectional study)	Drug: Definity Suspension for Injection; DEFINITY is administered as per manufactures instructions; 1 vial of DEFINITY is allowed to warm to room temperature and activated by 45s shaking on a VIALMIX; Withdraw the activated milky white suspension using the provided Dispensing Pin, PINSYNC or 18-20 gauge syringe needle, from the middle of the liquid in the inverted vial.; Deliver a dose of 10 μl/kg of 'milky white suspension' IV as a bolus, delivered over 30seconds.; Following imaging, provide a 10 mL flush of preservative-free saline; Wait at least 30minutes until second dose (if provided).; Other Names: DEFINITY
Group 1; SOP (healthy) subjects. Part I of study (optimizing protocol).	Drug: Definity Suspension for Injection; DEFINITY is administered as per manufactures instructions; 1 vial of DEFINITY is allowed to warm to room temperature and activated by 45s shaking on a VIALMIX; Withdraw the activated milky white suspension using the provided Dispensing Pin, PINSYNC or 18-20 gauge syringe needle, from the middle of the liquid in the inverted vial.; Deliver a dose of 10 μl/kg of 'milky white suspension' IV as a bolus, delivered over 30seconds.; Following imaging, provide a 10 mL flush of preservative-free saline; Wait at least 30minutes until second dose (if provided).; Other Names: DEFINITY
Group 2; Control (healthy and autoantibody positive) subjects. Part II of study (cross-sectional study)	Drug: Definity Suspension for Injection; DEFINITY is administered as per manufactures instructions; 1 vial of DEFINITY is allowed to warm to room temperature and activated by 45s shaking on a VIALMIX; Withdraw the activated milky white suspension using the provided Dispensing Pin, PINSYNC or 18-20 gauge syringe needle, from the middle of the liquid in the inverted vial.; Deliver a dose of 10 μl/kg of 'milky white suspension' IV as a bolus, delivered over 30seconds.; Following imaging, provide a 10 mL flush of preservative-free saline; Wait at least 30minutes until second dose (if provided).; Other Names: DEFINITY

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome 1	Optimized a contrast-enhanced ultrasound 'destruction-replenishment' protocol for imaging pancreas blood flow kinetics in adult human subjects.	End of part I (6 months)
Primary outcome 2	Comparison of pancreas blood flow kinetics (i.e. 'destruction-replenishment' k2 'reperfusion rate' parameter) between control and T1D subjects.	End of part II (1 year)
Primary outcome 3	Determining inter-subject variability in pancreas blood flow kinetics (i.e. the 'destruction-replenishment' k2 'reperfusion rate' parameter) among control subjects and among T1D subjects	End of part II (1 year)
Primary outcome 4	Determining reproducibility in the measurement of pancreas blood flow kinetics (i.e. the 'destruction-replenishment' k2 'reperfusion rate' parameter) within subjects. This will initially focus on short-term intra-subject measurement variability.	End of part II (1 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary outcome 1	Comparison between control and T1D subjects for other parameters resulting from the measurement of pancreas blood flow kinetics (i.e. the 'destruction-replenishment' 'reperfusion amplitude' A, 'destruction efficiency' 1-B and 'pre-destruction signal' parameters).	End of part II (1 year)
Secondary outcome 2	Determining inter-subject variability among control subjects and among T1D subjects for other parameters resulting from the measurement of pancreas blood flow kinetics (i.e. the 'destruction-replenishment' 'reperfusion amplitude' A, 'destruction efficiency' 1-B and 'pre-destruction signal' parameters).	End of part II (1 year)
Secondary outcome 3	Correlation of pancreas blood flow kinetics with blood glucose and HbA1c (to test for a link between the measurement and glucose control).	End of part II (1 year)
Secondary outcome 4	Comparison of pancreas blood flow kinetics with HLA haplotype or whether subject has first-degree relative with T1D (to test for a link between the measurement and T1D genetic risk).	End of part II (1 year)
Secondary outcome 5	Comparison of pancreas blood flow kinetics with subject BMI, age, heart rate, blood pressure (to test for a link between the measurement and subject characteristics)	End of part II (1 year)
Secondary outcome 6	Assessment of subject autoantibodies, c-peptide levels (to ensure subjects free of diabetes do not have islet autoimmunity and to ensure subjects with T1D have islet autoimmunity and residual beta cell mass)	End of part II (1 year)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Richard KP Benninger, PhD, University of Colorado - Anschutz Medical Campus

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: diabetes; ultrasound; pancreas; contrast; tissue perfusion
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Pancreatic Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Pancreatitis
• Other Study ID Numbers: 19-1543

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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