The Effects Of Bronchodilator Therapy On Respiratory And Autonomic Function In Patients With Familial Dysautonomia
Condition: Familial Dysautonomia
MeSH terms: Primary Dysautonomias; Autonomic Nervous System Diseases; Dysautonomia, Familial
Intervention: Albuterol-sulphate; Ipratropium-bromide; placebo
Intervention description: Beta-2-adrenergic agonist 2.5 mg 3 cc inhalation Peak effect 15 - 30 mins. Mean duration of effect 3 hours; Anti-cholinergic 500 mcg 3 cc inhalation Peak effect 30 - 90 mins. Duration of effect 2 - 4 hours.; Saline solution 3 cc NA
Intervention MeSH terms: Bromides; Albuterol; Ipratropium
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 15.0
Sex: All
Minimum age: 12 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: familial dysautonomia

Summary:

      Evaluate the effects of bronchodilator therapy on respiratory function. Our overall goal is
      to determine whether, in patients with familial dysautonomia (FD), there is a component of
      airway obstruction that is reversible. To this end, we will evaluate airway resistance before
      and after receiving the anti-cholinergic ipratropium (Atrovent ®) and the beta-2-agonist
      albuterol (ProVentil®/Ventolin®). We predict that the response to either drug will depend on
      the underlying level of sympathetic and parasympathetic activity and airway tone. We will
      then determine the cardiovascular effects of inhaled ipratropium and albuterol in patients
      with FD. Because patients with FD have fewer sympathetic neurons and denervation
      supersenstivity, we predict that following albuterol inhalation, there will be non-selective
      activation of alpha-1-adrenergic receptors. Furthermore, because of a congenital defect in
      the afferent baroreceptor neurons that sense blood pressure, we suspect that the resulting
      vasoconstriction will be unopposed leading to a pressor effect. We hypothesize that
      inhalation of the anti-cholinergic ipratopium will produce little rise in heart rate, due to
      the extent of parasympathetic denervation to the heart.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Diagnosis of familial dysautonomia (Riley-Day syndrome, hereditary sensory and
             autonomic neuropathy type III) 2. Ages 12 and older: Bronchodilators are routinely
             used in young children with FD therefore they should be included in this study. The
             spirometry maneuver is highly dependent on patient cooperation and effort, and FD
             patients already have limitations that make the spirometry maneuver more problematic
             to perform such as difficulty with mouth closure and drooling. Therefore, we believe
             age 12 is a suitable age for FD patients to be included in this study, though in the
             general population reliable results can be obtained from the age of 6 and sometimes
             even younger.

             3. Patients using Albuterol or Ipratroprium will be included in the study but will be
             instructed not to take the 24 hours prior to the testing. It is a common practice in
             clinical medicine to withhold the inhalation drugs prior to performing pulmonary
             function tests in order to evaluate the response to bronchodilators, an integral part
             of the test. Patients with an acute respiratory exacerbation will not be enrolled, as
             withholding bronchodilators would not be advisable.

             4. Patients who are taking medications that might affect autonomic function such as
             anti-hypertensives, beta-blockers, midodrine and florinef will be included in the
             study and we will record current medication regimen and the time the medication was
             taken.

        Exclusion Criteria:

        - 1. Patients who last used inhaled anti-cholinergics or beta-2-agonists within 4-half
        lives of the drug.

        2. Patients with an acute respiratory illness 3. Patients who have had lobectomies. 4.
        Patients using oxygen therapy throughout the day. 5. Patients who are unable to comply with
        the study requirements.