Propranolol in Treating Hypoglycemia Unawareness
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia
Intervention: Propranolol 80 Mg Oral Capsule, Extended Release; Placebo oral capsule
Intervention description: Propranolol capsule over-encapsulated to match placebo for blinding; Placebo capsule over-encapsulated to match propranolol for blinding
Intervention MeSH terms: Propranolol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2.0
Sex: All
Minimum age: 21 Years
Maximum age: 59 Years
Healthy volunteers: No
Keywords: Hypoglycemia; Impaired Awareness of Hypoglycemia; Propranolol

Summary:

      Impaired awareness of hypoglycemia is common in type 1 diabetes (T1DM) patients. Impaired
      hypoglycemia awareness increases severe hypoglycemia risk by six-fold. Severe hypoglycemia
      compromises quality of life and can potentially cause death. The long-term goal of this pilot
      study is to lead to the development of novel therapeutic approaches to improve hypoglycemia
      awareness and thus prevent severe hypoglycemia development in T1DM population with impaired
      awareness of hypoglycemia.

      It is hypothesized that propranolol will improve hypoglycemia recognition in T1DM. The
      specific aims of the study are to determine whether propranolol treatment improves subjects'
      recognition of hypoglycemic episodes, and improves hypoglycemic awareness scores; whether
      propranolol favorably increases hypoglycemia blood glucose nadir, decreases
      onset-to-treatment/recovery time (i.e. hypoglycemia duration), and reduces
      hypoglycemia/severe hypoglycemia frequency; and, whether propranolol reduces fear of
      hypoglycemia and improves overall blood glucose control.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with Type 1 diabetes mellitus for more than 5 years with impaired awareness
             of hypoglycemia

          -  Age between 21 to 59 years old

          -  Hemoglobin A1c ≤ 9%; most recent value within 3 months

          -  No beta-blocker use history in the last 6 months

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines

        Exclusion Criteria:

          -  History of coronary, cerebral or peripheral vascular disease

          -  History of cardiac conduction abnormality or heart failure

          -  History of advanced liver disease

          -  Active malignancy

          -  Major Central or Peripheral Nervous System disease

          -  History of human immunodeficiency virus infection

          -  Contraindication to beta-blockers, including hypersensitivity to beta-blocker and
             bronchospastic disease

          -  Female in pregnancy or not able to practice effective contraception during the study
             period

          -  Concomitant acetaminophen use

          -  Currently utilizing unblinded real-time continuous glucose monitoring

          -  Advanced diabetic microvascular complications including retinopathy, neuropathy and
             nephropathy

          -  Inability to understand or cooperate with study procedure, including performing
             glucometer glucose assessment a minimum of four times a day, carrying glucose tablets
             and following standardized hypoglycemia treatment, completing hypoglycemia diary,
             wearing continuous glucose monitoring, and using a single glucometer

          -  Recent or current use or involvement in clinical studies of other therapies (e.g.
             opioid antagonist, SSRI, behavioral modification, relaxation of glycemic control) that
             may improve hypoglycemia awareness or prevent impaired hypoglycemia awareness
             development