The Effects Of Bronchodilator Therapy On Respiratory And Autonomic Function In Patients With Familial Dysautonomia

NCT01987219 | Completed Phase 3 Results DMC

• 1 other identifier: 13-00004
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Familial Dysautonomia

Keywords

familial dysautonomia

Outcome Measures

Primary Outcomes (2)

• Change From Baseline of Forced Vital Capacity

  FVC is a measure of the amount of air exhaled, and is measured in liters of air per second. The percentage in the change in the amount of air exhaled from baseline, measured in liters of air per second. Increase in the percentage of air exhaled from baseline indicates improvement in respiratory function.

  Pre and 30 minutes post study drug administration

• Change in Respiratory Function (Airway Resistance at 5 Hz) From Baseline

  The percentage change in respiratory function from baseline is measured in percentage change in Resistance, kPa/(L/s).

  Pre and 30 minutes post study drug administration

Secondary Outcomes (2)

• Change in Forced Expiratory Volume (FEV) From Baseline

  Pre and 30 post study drug admistration

• Change in Forced Expiratory Flow Between 25-75% (FEF25-75)

  pre and 30 minutes post intervention

Study Arms (3)

Albuterol-sulphate

ACTIVE COMPARATOR

Albuterol-sulphate (Proventil ®) Beta-2-adrenergic agonist 2.5 mg 3 cc inhalation Peak effect 15 - 30 mins. Mean duration of effect 3 hours

Drug: Albuterol-sulphate

Ipratropium-bromide (Atrovent ®)

ACTIVE COMPARATOR

IpratroAnti-cholinergic(Atrovent ®) 500 mcg 3 cc inhalation Peak effect 30 - 90 mins. Duration of effect 2 - 4 hours.pium-bromide

Drug: Ipratropium-bromide

Placebo

PLACEBO COMPARATOR

Placebo Saline solution 3 cc NA

Other: placebo

Interventions

Albuterol-sulphate DRUG

Beta-2-adrenergic agonist 2.5 mg 3 cc inhalation Peak effect 15 - 30 mins. Mean duration of effect 3 hours

Also known as: (Proventil ®)

Albuterol-sulphate

Ipratropium-bromide DRUG

Anti-cholinergic 500 mcg 3 cc inhalation Peak effect 30 - 90 mins. Duration of effect 2 - 4 hours.

Also known as: (Atrovent ®)

Ipratropium-bromide (Atrovent ®)

placebo OTHER

Saline solution 3 cc NA

Placebo

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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.
• \. 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.

You may not qualify if:

• \- 1. Patients who last used inhaled anti-cholinergics or beta-2-agonists within 4-half lives of the drug.
• \. 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.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Dysautonomia, Familial

Interventions

Albuterol; Ipratropium

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hereditary Sensory and Autonomic Neuropathies; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Dr. Horacio Kaufmann
• Organization: NYU School of Medicine

horacio.kaufmann@nyumc.org

212 263 7225

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: November 19, 2013
• Study Start: March 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 2, 2016
• Results First Posted: June 2, 2016

Record last verified: 2016-04

Locations

US (1)