Hypoxic Pulmonary Vasoconstriction Pilot Study

NCT03733470 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 2011017075R01HL112986
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the events leading to smoking-associated centrilobular and paraseptal emphysema are caused by a failure of the lungs' inherent mechanisms to block hypoxic pulmonary vasoconstriction (HPV) in areas of smoking-induced inflammation.

Conditions

Emphysema

Outcome Measures

Primary Outcomes (1)

• Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration

  Perfused blood volume will be measured by CT scan at two time points and compared at two points, pre and post the administration of sildenafil.

  Change of perfused blood volume from baseline at one hour after sildenafil administration.

Study Arms (2)

Nonsusceptible Smokers (NS)

EXPERIMENTAL

8 subjects recruited to study non-contrast imaging at TLC and 20%VC and with contrast using DECT to assess perfused blood volume. For the intervention, the subject will be administered 20 mg of Sildenafil and then the same scanning will be repeated one hour after sildenafil administration.

Drug: Sildenafil study group

Susceptible Smokers (SS)

EXPERIMENTAL

11 subjects recruited to study non-contrast imaging at TLC and 20% VC and with contrast using DECT to assess pefused blood volume. For the intervention the subject will be administered 20 mg of Sildenafil and then the same scanning will be repeated one hour after sildenafil administration.

Drug: Sildenafil study group

Interventions

Sildenafil study group DRUG

One dose of 20 mg Sildenafil will be given one hour before CT imaging.

Also known as: Revatio

Nonsusceptible Smokers (NS); Susceptible Smokers (SS)

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be between the ages of 30 and 60.
• Must be currently smoking at least 1/2 pack/day (confirmed with cotinine level).
• Must have pulmonary function test (PFT) results that meet the following:
• Forced Expiratory Volume at one second (FEV1)/Forced Vital Capacity (FVC) \> 70%
• Forced Expiratory Flow at 25-75% (FEF25-75) \> 79% of predicted
• FVC greater than 80% of predicted
• Must be able to give informed consent for self.

You may not qualify if:

• Pregnant or breastfeeding females.
• Body Mass Index (BMI) greater than 32.
• Weight of greater than 220 pounds (100 kg).
• Allergies to shell fish, seafood, eggs or iodine.
• Heart disease, kidney disease or diabetes.
• Diagnosis of asthma.
• Usage of any medications that are known to affect the heart or lungs (contraceptives, anti-depressants, analgesics EXCEPT aspirin, antihypertensives, and medications for osteoporosis and gastrointestinal diseases will be allowed).
• Any metal in or on the body between the nose and the abdomen.
• Any major organ system disease (by judgment of study medical team).
• Nitroglycerin usage.
• Prior history of hypersensitivity to Sildenafil.

Sponsors & Collaborators

• Eric A. Hoffman: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• Alford SK, van Beek EJ, McLennan G, Hoffman EA. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7485-90. doi: 10.1073/pnas.0913880107. Epub 2010 Apr 5.

  PMID: 20368443 RESULT

MeSH Terms

Conditions

Emphysema

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Eric Hoffman, PhD
• Organization: University of Iowa

eric-hoffman@uiowa.edu

319-365-1381

Study Officials

• Eric A Hoffman

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: November 7, 2018
• Study Start: June 29, 2011
• Primary Completion: January 13, 2014
• Study Completion: January 13, 2014
• Last Updated: October 1, 2019
• Results First Posted: October 1, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available starting 6 months after publication of the primary results of each aim.
• Access Criteria: Data will be provided to academic-based researchers upon written request to the PI, Eric A. Hoffman, Ph.D. A nominal charge will be made for the time it takes for a technician to prepare and transfer the requested data. This costs will not exceed $250. This service will be available for a minimum of 2 years of study close.

Locations

US (1)