Restoring low-blood-sugar awareness with closed-loop pumps or targeted education
Closed Loop and Education for Hypoglycemia Awareness Restoration (CLEAR), Conducted by the Impaired Awareness of Hypoglycemia Consortium (IAHC)
This study will test whether using hybrid closed-loop insulin systems or focused education can help adults with type 1 diabetes who no longer notice low blood sugar regain their awareness.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 324 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Milton S. Hershey Medical Center Academic / other |
| Locations | 8 sites (La Jolla, California and 7 other locations) |
| Trial ID | NCT06325202 on ClinicalTrials.gov |
What this trial studies
Adults with long-duration type 1 diabetes and impaired awareness of hypoglycemia are assigned to use an advanced hybrid closed-loop system (Omnipod 5 or Medtronic 780G) or to participate in one of two structured education programs (My HypoCOMPaSS or HARPdoc). The primary outcome is change in counterregulatory hormonal and symptomatic responses to low blood sugar measured using experimental hypoglycemia clamp testing. The trial is conducted at multiple U.S. centers and includes behavioral and technology-based approaches to reduce hypoglycemia exposure. The study will also examine whether participant characteristics influence which intervention works best.
Who should consider this trial
Good fit: Adults with type 1 diabetes of at least 10 years' duration who have impaired awareness of hypoglycemia (Gold or Clarke score ≥4), low C‑peptide (<200 pmol/L), HbA1c <10.5%, and total daily insulin dose <1 unit/kg who can read and speak English are ideal candidates.
Not a fit: People without impaired hypoglycemia awareness, with significant medical or cognitive conditions that limit participation, active substance abuse, or who do not meet the biochemical/insulin criteria (for example C‑peptide ≥200 pmol/L or insulin ≥1 unit/kg) are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the interventions could help people regain warning symptoms of low blood sugar and reduce episodes of severe hypoglycemia.
How similar studies have performed: Previous work shows CGM and hybrid closed-loop systems reduce severe hypoglycemia and behavioral education can lower hypoglycemia rates, but it remains unclear from prior studies whether these approaches reverse counterregulatory deficits, and direct comparisons are limited.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
La Jolla, California and 7 other locations
- University of California, San Diego — La Jolla, California, United States (Recruiting)
- AdventHealth — Orlando, Florida, United States (Recruiting)
- University of Kentucky — Lexington, Kentucky, United States (Recruiting)
- University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
- University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
- University of Melbourne — Fitzroy, Victoria, Australia (Recruiting)
- University of Leicester — Leicester, United Kingdom (Recruiting)
- University of Sheffield — Sheffield, United Kingdom (Recruiting)
Study contacts
- Principal investigator: Vernon M Chinchilli, PhD — Penn State College of Medicine
- Study coordinator: Abid Kazi, PhD
- Email: akazi@pennstatehealth.psu.edu
- Phone: 717-531-0003
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.