Recruiting

Hypoglycemia Awareness

Sponsor:

Milton S. Hershey Medical Center

Code:

NCT06325202

Conditions

Diabetes Mellitus, Type 1

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Omnipod 5 or Medtronic 780G

My HypoCOMPaSS Education

HARPdoc Education

Study Details

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.

Conditions

Diabetes Mellitus, Type 1

Study ID

NCT06325202

Start date

Oct 3, 2025

Status verified date

Feb, 2026

Completion date

Jul 31, 2029

Anticipated

Primary completion date

Jul 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • History of adrenalectomy

  • At discretion of the PI, laboratory tests may be repeated once. If the participant is not eligible after the second attempt, then the participant. The participant may be screened again.

Study Design

Enrollment

324 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: current HCL non-user: HCL x 24 months

Hybrid closed loop device over a 24-month period for individuals currently not using a hybrid closed loop device

experimental: current HCL non-user: HCL x 12 months, then HCL x an additional 12 months

Hybrid 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

experimental: current HCL non-user: HCL x 12 months, then HCL + HARPdoc x 12 months

Hybrid 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

active comparator: current HCL non-user: Usual Care and My HypoCOMPaSS x 12 months, then HCL x 12 months

Usual 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

active comparator: current HCL non-user: Usual Care and My HypoCOMPaSS x 24 months

Usual Care and My HypoCOMPaSS education over 24 months for individuals currently not using a hybrid closed loop device

experimental: current HCL user: HCL x 24 months

Hybrid closed loop device over a 24-month period for individuals currently using a hybrid closed loop device

experimental: current HCL user: HCL x 12 months, then HCL x an additional 12 months

Hybrid 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

experimental: current HCL user: HCL x 12 months, then HCL + HARPdoc x 12 months

Hybrid 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

active comparator: current HCL user: HCL and My HypoCOMPaSS x 12 months, then HCL x 12 months

Hybrid 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

active comparator: current HCL user: HCL + My HypoCOMPaSS x 12 months, then HCL + My HypoCOMPaSS + HARPDOC x 12 months

Hybrid 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

experimental: current HCL user: HCL + My HypoCOMPaSS x 24 months

Hybrid closed loop device plus My HypoCOMPaSS education over a 24-month period for individuals currently using a hybrid closed loop device

Interventions

Omnipod 5 or Medtronic 780G

Omnipod 5 and Medtronic 780G are hybrid closed loop devices that provide automated insulin delivery.

My HypoCOMPaSS Education

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.

HARPdoc Education

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.

Primary outcome measure

  • epinephrine (pg/ml) [ Time Frame: measured during the clamp studies at 0 (baseline), 12, and 24 months ]
  • Towler questionnaire [ Time Frame: measured during the clamp studies at 0 (baseline), 12, and 24 months ]

Central Contacts and Locations

Central contacts

Abid Kazi, PhD

717-531-0003akazi@pennstatehealth.psu.edu

Venus Grella, MPH

717-531-0003vgrella@pennstatehealth.psu.edu

Locations

University of California, San Diego

Recruiting

La Jolla, California, United States, 92037

Contacts

Jeremy H Pettus, MD

858-246-2160jpettus@ucsd.edu

Principal Investigator:

Jeremy H Pettus, MD

AdventHealth

Recruiting

Orlando, Florida, United States, 32804

Contacts

Brooke Hartwell

407-303-2519brooke.hartwell@adventhealth.com

Principal Investigator:

Richard E Pratley, MD

University of Kentucky

Recruiting

Lexington, Kentucky, United States, 40508

Contacts

Simon Fisher, MD, PhD

859-562-0473simon.fisher@uky.edu

Principal Investigator:

Simon Fisher, MD, PhD

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Sarah Zaun

612-301-7040studydiabetes@umn.edu

Principal Investigator:

Elizabeth R Seaquist, MD

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Cornelia (Ginger) Dalton-Bakes

215-746-2085corneliv@pennmedicine.upenn.edu

Principal Investigator:

Michael R Rickels, MD, MS

More Information

Sponsor

Milton S. Hershey Medical Center

Last update posted

Mar 3, 2026

Last verified

Feb, 2026

Keywords

  • impaired awareness of hypoglycemia
  • hybrid closed loop device
  • continuous glucose monitor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Milton S. Hershey Medical Center on 2026-03-03.