Pancreas Ultrasound Imaging in type1 Diabetes

Official title

Contrast Enhanced Ultrasound Imaging of Pancreas Blood Flow in type1 Diabetes

Overview

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.

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.

Interventions

• 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 sa

Primary outcome measures

• Primary outcome 1 [Time frame: End of part I (6 months)]
• Primary outcome 2 [Time frame: End of part II (1 year)]
• Primary outcome 3 [Time frame: End of part II (1 year)]
• Primary outcome 4 [Time frame: End of part II (1 year)]

Secondary outcome measures (6)

• Secondary outcome 1 [Time frame: End of part II (1 year)]
• Secondary outcome 2 [Time frame: End of part II (1 year)]
• Secondary outcome 3 [Time frame: End of part II (1 year)]
• Secondary outcome 4 [Time frame: End of part II (1 year)]
• Secondary outcome 5 [Time frame: End of part II (1 year)]
• Secondary outcome 6 [Time frame: End of part II (1 year)]

Eligibility criteria

All Participants:

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)

Group 2 (control subjects, part II):

Inclusion criteria

No additional inclusion criteria

Exclusion criteria

• Diagnosis of diabetes according to the ADA recommended criteria (blood glucose and HbA1c will be measured)
• Use of medications used to control high blood sugar (GLP1R agonists, metformin\*, sulfonylureas)

• \*Participants taking metformin will be considered eligible if they are willing/able to stop taking the medication for at least two weeks prior to each scan.
• Any person who has received immunomodulatory intervention within 3 months of enrollment

Group 3 (T1D subjects, part II)

Inclusion criteria

• Diagnosis of diabetes according to the ADA recommended criteria (blood glucose and HbA1c will be measured)
• Evidence of autoantibodies to at least 1 of the following β-cell autoantigens:

insulin, IA-2, GAD65, ZnT8

• Presence of insulin autoantibody will only be valid if taken within the first 14 days of diagnosis.

• Diagnosis of diabetes within 180 days prior to participation in the study

Exclusion criteria

• Use of medications used to control high blood sugar (GLP1R agonists, metformin\*, sulfonylureas)

• \*Participants taking metformin will be considered eligible if they are willing/able to stop taking the medication for at least two weeks prior to each scan.
• Any person who has received immunomodulatory intervention within 3 months of enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

United States · 1 center

• University of Colorado Anschutz, Barbara Davis Center — Aurora

Identifiers

NCT: NCT05482321 · 19-1543

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗