Amitriptyline in Treating Hypoglycemia
Condition: Type1 Diabetes Mellitus; Hypoglycemia Unawareness
MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia
Intervention: Amitriptyline; Placebo
Intervention description: Participants will receive a supply of Amitriptyline capsules for titration, intervention, and taper periods.; Participants will receive a supply of Placebo capsules, matching those of Amitriptyline, for the titration, intervention, and taper periods
Intervention MeSH terms: Amitriptyline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-blind, randomized, placebo control
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2.0
Sex: All
Minimum age: 21 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      Patients with type 1 diabetes mellitus (T1DM) commonly experience hypoglycemia and develop
      impaired awareness of hypoglycemia. Many patients using continuous glucose monitoring (CGM)
      system to mitigate these complications, but continue to spend a significant amount of time in
      hypoglycemia. The long-term goal is to develop novel and readily available therapeutic
      approaches to improve hypoglycemia course and awareness in T1DM patients. The objective of
      this study is to determine whether amitriptyline will improve hypoglycemia course and the
      ability to recognize hypoglycemic events in T1DM patients who are using CGM.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with Type 1 Diabetes Mellitus for at least 5 years or more

          -  Age between 21 to 60 years old

          -  HbA1c less or equal to 9% with the latest measurement within the last 3 months

          -  Use of real time Continuous Glucose Monitoring (rtCGM) providing continuous glucose
             data points for at least 3 months, and at least 80% of CGM readings available over the
             last 2-week period

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines

        Exclusion Criteria:

          -  Ongoing or recent history of major depressive disorder, or other ongoing major
             psychiatric disorders

          -  History of anti-depressant use within the last three months

          -  Insulin pump linked to a CGM with programmed automatic insulin adjustment or
             suspension

          -  History of advanced cardiac, liver, kidney or neurological disease

          -  Active malignancy

          -  Uncontrolled Human Immunodeficiency Virus diseases

          -  Advanced diabetic retinopathy, neuropathy, or nephropathy

          -  Frequent acetaminophen use which can disrupt CGM accuracy

          -  Pregnancy or female of child-bearing potential unable to practice effective
             contraception during the study period

          -  Breastfeeding female, or female with prospective plan to initiate breastfeeding

          -  Ongoing history of alcohol abuse

          -  Contraindication to amitriptyline use, including hypersensitivity to amitriptyline or
             any component of the formulation, co-administration with or within 14 days of
             Monoamine Oxidase Inhibitors and co-administration with cisapride

          -  Inability to understand or cooperate with study procedures, including taking study
             drugs and recording hypoglycemic symptoms.

        The participants meeting the above criteria will enter "Run-in Period". At the Visit 2, the
        following additional exclusion criteria will be applied before study drug randomization:

          -  < 80% of CGM readings available over the last 2-week period

          -  Time spent in hypoglycemia (i.e., < 70 mg/dL) for < 5% over a 2-week period on based
             on CGM reading.