Closed Loop and Education for Hypoglycemia Awareness Restoration
CLEAR
2 other identifiers
interventional
324
3 countries
8
Brief Summary
The purpose of the CLEAR study is to determine the effect on counterregulatory responses (CRR) of intervening (by attempting to strictly avoid hypoglycemia) to improve awareness of hypoglycemic symptoms among adults with type 1 diabetes (T1D) who have impaired awareness of hypoglycemia (IAH). IAH affects 20-25% of adults with T1D, and rises with increasing duration of T1D.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Oct 2025
Longer than P75 for not_applicable
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 5, 2024
CompletedFirst Posted
Study publicly available on registry
March 22, 2024
CompletedStudy Start
First participant enrolled
October 3, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2029
March 3, 2026
February 1, 2026
3.8 years
March 5, 2024
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
epinephrine (pg/ml)
a change in epinephrine (pg/ml) that exceeds 125 pg/ml between (1) 12 months and baseline, and (2) 24 months and baseline
measured during the clamp studies at 0 (baseline), 12, and 24 months
Towler questionnaire
the Towler questionnaire consists of 12 questions each on a 0-6 Likert scale; a change in the questionnaire that exceeds 20% between (1) 12 months and baseline, and (2) 24 months and baseline
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary Outcomes (39)
geometric mean of plasma glucagon
measured during the clamp studies at 0 (baseline), 12, and 24 months
geometric mean of plasma pancreatic polypeptide
measured during the clamp studies at 0 (baseline), 12, and 24 months
geometric mean of plasma free fatty acids
measured during the clamp studies at 0 (baseline), 12, and 24 months
glucose infusion rate
measured during the clamp studies at 0 (baseline), 12, and 24 months
HbA1c
measured during the clamp studies at 0 (baseline), 12, and 24 months
- +34 more secondary outcomes
Study Arms (11)
current HCL non-user: HCL x 24 months
EXPERIMENTALHybrid closed loop device over a 24-month period for individuals currently not using a hybrid closed loop device
current HCL non-user: HCL x 12 months, then HCL x an additional 12 months
EXPERIMENTALHybrid closed loop device over a 12-month period for individuals currently not using a hybrid closed loop device, and then a hybrid closed loop device for an additional 12 months
current HCL non-user: HCL x 12 months, then HCL + HARPdoc x 12 months
EXPERIMENTALHybrid closed loop device over a 12-month period for individuals currently not using a hybrid closed loop device, then a hybrid closed loop device plus HARPdoc education for an additional 12 months
current HCL non-user: Usual Care and My HypoCOMPaSS x 12 months, then HCL x 12 months
ACTIVE COMPARATORUsual Care and My HypoCOMPaSS education over 12 months for individuals currently not using a hybrid closed loop device, then hybrid closed loop device for 12 months
current HCL non-user: Usual Care and My HypoCOMPaSS x 24 months
ACTIVE COMPARATORUsual Care and My HypoCOMPaSS education over 24 months for individuals currently not using a hybrid closed loop device
current HCL user: HCL x 24 months
EXPERIMENTALHybrid closed loop device over a 24-month period for individuals currently using a hybrid closed loop device
current HCL user: HCL x 12 months, then HCL x an additional 12 months
EXPERIMENTALHybrid closed loop device over a 12-month period for individuals currently using a hybrid closed loop device, and then a hybrid closed loop device for an additional 12 months
current HCL user: HCL x 12 months, then HCL + HARPdoc x 12 months
EXPERIMENTALHybrid closed loop device over a 12-month period for individuals currently using a hybrid closed loop device, then a hybrid closed loop device plus HARPdoc education for an additional 12 months
current HCL user: HCL and My HypoCOMPaSS x 12 months, then HCL x 12 months
ACTIVE COMPARATORHybrid closed loop device and My HypoCOMPaSS education over 12 months for individuals currently using a hybrid closed loop device, then hybrid closed loop device for 12 months
current HCL user: HCL + My HypoCOMPaSS x 12 months, then HCL + My HypoCOMPaSS + HARPDOC x 12 months
ACTIVE COMPARATORHybrid closed loop device and My HypoCOMPaSS education over 12 months for individuals currently using a hybrid closed loop device, then hybrid closed loop device plus My HypoCOMPaSS eduction + HARPdoc education for 12 months
current HCL user: HCL + My HypoCOMPaSS x 24 months
EXPERIMENTALHybrid closed loop device plus My HypoCOMPaSS education over a 24-month period for individuals currently using a hybrid closed loop device
Interventions
Omnipod 5 and Medtronic 780G are hybrid closed loop devices that provide automated insulin delivery.
My HypoCOMPaSS is a brief, standardized psycho-educational program delivered in small groups. Facilitated discussions focus on advocating rigorous avoidance of hypoglycemia while maintaining time in target glycemic range.
The HARPdoc program targets cognitions around hypoglycemia that act as barriers to hypoglycemia avoidance and recovery of awareness using motivational and cognitive approaches, delivered by diabetes educators, trained and supported by a clinical psychologist, in small group format.
Eligibility Criteria
You may qualify if:
- Clinical diagnosis of type 1 diabetes
- Gold Score or Clarke Score ≥ 4 (highly associated with IAH)
- Random non-fasting C-peptide \< 200 pmol/L
- Diabetes duration ≥ 10 years
- HbA1c \< 10.5%
- Total Daily Insulin Dose of \< 1 unit/kg
- Ability to read and speak English (because validated non-English versions of the cognitive tests and the educational interventions are not available)
You may not qualify if:
- Medical conditions that limit participation in study activities, as determined by the PI (including but not limited to cognitive dysfunction, reduced hearing, reduced vision, cancer under active treatment, untreated angina, organ failure)
- Active alcohol or drug abuse (as defined by DSM criteria of either 1) recurrent use of alcohol/drugs resulting in a failure to fulfill major role obligations at work, school, or home, 2) recurrent alcohol/drug use in situations in which it is physically hazardous, or 3) recurrent alcohol or drug-related legal problems)
- Social determinants of health that limit participation in study activities, as determined by the PI (including but not limited to homelessness, food insecurity, inadequate social support)
- Seizure disorder unrelated to hypoglycemia associated seizures, unless documented seizure-free for \>12 months and on a stable regimen of anti-convulsant therapy
- Skin conditions that would preclude the use of a CGM
- Super-physiologic exposure to steroids within one month of enrollment
- eGFR \< 45 mL/min/1.73 m2
- History of bariatric surgery that irreversibly alters gut innervation and structure
- Hyper- or hypokalemia (serum potassium \>5.5 or \<3.5 mmol/L)\*
- Hemoglobin \< 10 g/dL\*
- Medical condition that requires intermittent or continuous use of glucocorticoids at greater than physiological replacement doses
- Pregnancy, plan for pregnancy, or breast feeding
- Abnormal thyroid function tests of clinical significance, as determined by PI\*
- Liver transaminases \> 3 times the upper limit of normal\*
- Hospitalization for mental illness in last year
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Milton S. Hershey Medical Centerlead
- University of Minnesotacollaborator
- University of Kentuckycollaborator
- University of Pennsylvaniacollaborator
- AdventHealthcollaborator
- University of Leicestercollaborator
- University of Sheffieldcollaborator
- University of Melbournecollaborator
- Jaeb Center for Health Researchcollaborator
- University of California, San Diegocollaborator
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)collaborator
Study Sites (8)
University of California, San Diego
La Jolla, California, 92037, United States
AdventHealth
Orlando, Florida, 32804, United States
University of Kentucky
Lexington, Kentucky, 40508, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Melbourne
Fitzroy, Victoria, 3065, Australia
University of Leicester
Leicester, LE5 4PW, United Kingdom
University of Sheffield
Sheffield, S10 2RX, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Vernon M Chinchilli, PhD
Penn State College of Medicine
- STUDY CHAIR
Elizabeth R Seaquist, MD
University of Minnesota
- STUDY CHAIR
Simon Heller, MD
University of Sheffield
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Distinguished Professor
Study Record Dates
First Submitted
March 5, 2024
First Posted
March 22, 2024
Study Start
October 3, 2025
Primary Completion (Estimated)
July 31, 2029
Study Completion (Estimated)
July 31, 2029
Last Updated
March 3, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- The timeline for data sharing from the Impaired Awareness of Hypoglycemia Consortium will meet NIH data sharing requirements, such as one year after the Consortium investigators have published the primary manuscript. The Biostatistics Research Center at the Penn State College of Medicine will make data available after the acceptance for publication of the main findings that address the specific aims of the study.
- Access Criteria
- Investigators external to the Consortium will be able to request the data from the NIDDK Central Repository. They will be required to show proof of their local IRB approval.
The release data sets will be stored at the NIDDK Central Repository. The release data sets will de-identified, i.e., they will not contain names, social security numbers, addresses, phone numbers, health care records, and/or similar protected health information. In addition, the release data sets will have an anonymous study ID that is linked to an individual only in the participant records at the Biostatistics Research Center at the Penn State College of Medicine.