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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06325202




Registration number
NCT06325202
Ethics application status
Date submitted
5/03/2024
Date registered
22/03/2024

Titles & IDs
Public title
Closed Loop and Education for Hypoglycemia Awareness Restoration
Scientific title
Closed Loop and Education for Hypoglycemia Awareness Restoration (CLEAR), Conducted by the Impaired Awareness of Hypoglycemia Consortium (IAHC)
Secondary ID [1] 0 0
1U01DK135126
Secondary ID [2] 0 0
STUDY00020946
Universal Trial Number (UTN)
Trial acronym
CLEAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Omnipod 5 or Medtronic 780G
BEHAVIORAL - My HypoCOMPaSS Education
BEHAVIORAL - HARPdoc Education

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


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

BEHAVIORAL: 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.

BEHAVIORAL: 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.
Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
BEHAVIORAL
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
epinephrine (pg/ml)
Timepoint [1] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Primary outcome [2] 0 0
Towler questionnaire
Timepoint [2] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [1] 0 0
geometric mean of plasma glucagon
Timepoint [1] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [2] 0 0
geometric mean of plasma pancreatic polypeptide
Timepoint [2] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [3] 0 0
geometric mean of plasma free fatty acids
Timepoint [3] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [4] 0 0
glucose infusion rate
Timepoint [4] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [5] 0 0
HbA1c
Timepoint [5] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [6] 0 0
% of time with sensor hypoglycemia <70 mg/dL
Timepoint [6] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [7] 0 0
% of time with sensor hypoglycemia <54 mg/dL
Timepoint [7] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [8] 0 0
number of hypoglycemia events
Timepoint [8] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [9] 0 0
% time with sensor glucose in range
Timepoint [9] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [10] 0 0
sensor glucose coefficient of variation
Timepoint [10] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [11] 0 0
sensor use as the average numbers of days per week
Timepoint [11] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [12] 0 0
glycemia risk index
Timepoint [12] 0 0
measured during the four weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [13] 0 0
Trail Making Test - Part B
Timepoint [13] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [14] 0 0
Four Choice Reaction Time
Timepoint [14] 0 0
measured during the clamp studies at 0 (baseline), 12, and 24 months
Secondary outcome [15] 0 0
sleep duration
Timepoint [15] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [16] 0 0
sleep quality
Timepoint [16] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [17] 0 0
24-hour step count
Timepoint [17] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [18] 0 0
exercise bouts
Timepoint [18] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [19] 0 0
resting heart rate
Timepoint [19] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [20] 0 0
heart rate during exercise
Timepoint [20] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [21] 0 0
heart rate variability
Timepoint [21] 0 0
measured during the two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [22] 0 0
Hypo-METRICS questionnaire
Timepoint [22] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [23] 0 0
Hypoglycemic Confidence Scale
Timepoint [23] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [24] 0 0
Hypoglycemia Fear Survey-II
Timepoint [24] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [25] 0 0
Attitudes to Awareness of Hypoglycaemia
Timepoint [25] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [26] 0 0
Type 1 Diabetes Distress Scale
Timepoint [26] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [27] 0 0
Diabetes Self-Management Questionnaire
Timepoint [27] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [28] 0 0
Diabetes Management Experiences Questionnaire
Timepoint [28] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [29] 0 0
PROMIS Sleep Disturbance - Short Form 8a
Timepoint [29] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [30] 0 0
Hospital Anxiety and Depression Scale
Timepoint [30] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months, the range is 0 through 42 and higher scores correspond to higher anxiety and depression
Secondary outcome [31] 0 0
12-Item Hypoglycemia Impact Profile
Timepoint [31] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [32] 0 0
EQ-5D-5L
Timepoint [32] 0 0
measured two weeks prior to each clamp study at 0 (baseline), 12, and 24 months
Secondary outcome [33] 0 0
device-related adverse events
Timepoint [33] 0 0
throughout the duration of the 24 months of follow-up
Secondary outcome [34] 0 0
severe hypoglycemic events, self-reported on a CLEAR data collection form
Timepoint [34] 0 0
throughout the duration of the 24 months of follow-up
Secondary outcome [35] 0 0
diabetic ketoacidosis (DKA) events
Timepoint [35] 0 0
throughout the duration of the 24 months of follow-up
Secondary outcome [36] 0 0
number of participants with hospitalizations
Timepoint [36] 0 0
throughout the duration of the 24 months of follow-up
Secondary outcome [37] 0 0
number of participants with emergency room (ER) visits
Timepoint [37] 0 0
throughout the duration of the 24 months of follow-up
Secondary outcome [38] 0 0
major adverse cardiovascular events (MACE)
Timepoint [38] 0 0
throughout the duration of the 24 months of follow-up
Secondary outcome [39] 0 0
all-cause mortality
Timepoint [39] 0 0
throughout the duration of the 24 months of follow-up

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
NA
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
324
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
University of Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Leicester
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Other
Name
Milton S. Hershey Medical Center
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Minnesota
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Kentucky
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Pennsylvania
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
University of California, San Diego
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
AdventHealth
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
University of Leicester
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
University of Sheffield
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
University of Melbourne
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Jaeb Center for Health Research
Address [10] 0 0
Country [10] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vernon M Chinchilli, PhD
Address 0 0
Penn State College of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Abid Kazi, PhD
Address 0 0
Country 0 0
Phone 0 0
717-531-0003
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://repository.niddk.nih.gov/home/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06325202