Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia
Condition: Hereditary Hemorrhagic Telangiectasia
MeSH terms: Epistaxis; Telangiectasis; Telangiectasia, Hereditary Hemorrhagic
Intervention: Timolol Gel; Placebo Gel
Intervention description: Timolol nasal gel 0.1% will be prepared with a poloxamer gel (combination of poloxamer 188 and 407; pH adjusted to 4.5-6.5) and 0.5 ml applied to each nostril twice daily. The total daily dose would amount to 2 mg.; Placebo gel is prepared with poloxamers and no active ingredients.
Intervention MeSH terms: Timolol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Epistaxis

Summary:

      This study is a double-blinded, randomized controlled trial to evaluate the efficacy of an
      intranasal topical timolol gel in the care for epistaxis in adults with hereditary
      hemorrhagic telangiectasia.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults ages 20 and older

          2. Confirmed clinical (meeting at least 3 of the 4 Curaçao Criteria) or genetic diagnosis
             of HHT

          3. Epistaxis Severity Score (ESS) ≥ 4 and 2 or more nosebleeds per week with a cumulative
             nosebleed duration of at least 5 minutes per week

          4. Stable nasal hygiene and medical regimen for preceding 1 month

          5. Stable epistaxis pattern over the preceding 3 months

        Exclusion Criteria:

          1. Contraindications for systemic β adrenergic blocker administration

               1. Hypersensitivity to β adrenergic blockers

               2. Asthma or bronchospasm

               3. Congestive heart failure with LVEF <40%

               4. Hereditary pulmonary arterial hypertension

               5. Baseline bradycardia (HR <55 beats per minute)

               6. Sick Sinus Syndrome

               7. 2nd or 3rd degree heart block, left or right bundle branch block, or bifasicular
                  block

               8. Uncontrolled diabetes mellitus (most recent HbA1c >9%) or diabetic ketoacidosis
                  within last 6 months

               9. Hypotension (systolic blood pressure < 90)

          2. Known hypersensitivity to timolol

          3. Severe peripheral circulatory disturbances (Raynaud phenomenon)

          4. Known intermediate or poor metabolizer variant of the liver enzyme CYP2D6

          5. Current use of any of the following known strong CYP2D6 inhibitors: fluoxetine
             (Prozac), paroxetine (Paxil), bupropion (Welbutrin), quinidine, quinine, ritonavir
             (Norvir), and terbinafine (Lamisil)

          6. Current use of the following other drugs known to pharmacodynamically interact with
             timolol: diltiazem, verapamil, digoxin, digitalis, propafenone, disopyramide,
             clonidine, flecainide, or lidocaine

          7. Patients currently treated or who plan to initiate treatment with β-blockers

          8. Use of any anti-angiogenic medication in the last month prior to recruitment,
             including bevacizumab, pazopanib, thalidomide, or lenalidomide

          9. Illicit drug use, except marijuana

         10. Known pheochromocytoma

         11. Use of anticoagulants, antiplatelet, or fibrinolytic therapies within the last month
             prior to recruitment, except for low-dose (81 mg or less) of aspirin

         12. Pregnancy or planned pregnancy in the next 6 months or currently breastfeeding

         13. Inability to read or understand English

         14. Inability to complete 8 weeks of therapy for any reason