Carvedilol in Treating Hypoglycemia Unawareness
Condition: Hypoglycemia Unawareness
MeSH terms: Unconsciousness; Hypoglycemia
Intervention: Carvedilol 3.125 mg; Carvedilol 2.5 mg; Placebo capsule
Intervention description: Participants will receive a 3.125 mg oral dose of carvedilol twice daily during the 4-week treatment period; Participants will receive a 2.5 mg oral dose of carvedilol twice daily during the 4-week treatment period; Participants will receive a matching oral dose of placebo capsule twice daily during the 4-week treatment period
Intervention MeSH terms: Carvedilol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-blinded, randomized, placebo-controlled study in patients with Type 1 diabetes mellitus and hypoglycemia unawareness
Masking: Double (Participant, Investigator)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes Mellitus; β-blocker

Summary:

      Type 1 diabetes mellitus (T1DM) can lead to cardiovascular, renal and neurological
      complications if left poorly-controlled over prolonged periods of time. However, lowering
      glycemic goals for diabetic patients increases their risk for hypoglycemia exposure.
      Hypoglycemia is associated with symptoms such as heart palpitations, fatigue, shakiness,
      anxiety, confusion, and blurred vision. Recurrent hypoglycemia leads to impairment of the
      body's autonomic and symptomatic responses to this condition, and can result in loss of
      awareness in the patient of the hypoglycemic state. Repeated incidences of hypoglycemia from
      loss of this awareness can result in even more hypoglycemic episodes and more severe
      outcomes, such as loss of consciousness, accidents, hospitalization and even death if left
      untreated.

      The aim of this study is to investigate whether adrenergic blockade through the use of
      low-dose carvedilol treatment can improve hypoglycemia awareness and the counterregulatory
      hormone responses to hypoglycemia in T1DM patients with impaired awareness of hypoglycemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of Type 1 diabetes mellitus for more than 5 years

          -  Age > 18 years

          -  Presence of impaired hypoglycemia awareness/unawareness

          -  Intensive insulin treatment as defined by multiple daily insulin injections (3 or
             more) or insulin pump therapy

          -  Negative pregnancy test

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines

        Exclusion Criteria:

          -  Major medical disorders (including liver disease, cardiovascular disease, kidney
             disease, chronic obstructive pulmonary disease, asthma, active malignancy or HIV)

          -  Overt diabetes complications (neuropathy, nephropathy, retinopathy)

          -  Presence of anemia

          -  Current or recent use of beta-blocker therapy

          -  Use of diuretics

          -  Allergies or contraindications to beta-blockers or heparin

          -  Use of benzodiazepines

          -  Alcohol, drug or medication abuse

          -  Frequent use of acetaminophen