Is Blood Flow Through IPAVA and PFO Related to Breath-hold and SCUBA Diving-induced Pulmonary Hypertension?

NCT03945643 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 07302018.031
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

In summary, the investigators propose to study elite Croatian breath-hold and SCUBA divers. The investigators will quantify breath-hold hypoxia- and SCUBA diving-induced pulmonary hypertension and right heart function to investigate the relationships between PFO and IPAVA blood flow. The investigators will use a placebo-controlled intervention (sildenafil) to reduce pulmonary arterial pressure in these subjects to examine the impact of the change in pressure (or absence of change) on the relationships determined above.

Conditions

Patent Foramen Ovale; Intrapulmonary Arteriovenous Anastamosis

Outcome Measures

Primary Outcomes (14)

• Pulmonary Pressure

  Pulmonary arterial pressure measured by ultrasound techniques

  1 hour post intervention

• Concentration of Myoglobin

  Inflammatory cytokine

  1 hour post intervention

• Concentration of MRP8/14

  Inflammatory cytokine

  1 hour post intervention

• Concentration of NGAL

  Inflammatory cytokine

  1 hour post intervention

• Concentration Of CRP

  Inflammatory cytokine

  1 hour post intervention

• Concentration Of MMP-2

  Inflammatory cytokine

  1 hour post intervention

• Concentration of OPN

  Inflammatory cytokine

  1 hour post intervention

• Concentration Of SAA

  Inflammatory cytokine

  1 hour post intervention

• Concentration of IGFBP-4

  Inflammatory cytokine

  1 hour post intervention

• Concentration of ICAM-1

  Inflammatory cytokine

  1 hour post intervention

• Concentration of VCAM-1

  Inflammatory cytokine

  1 hour post intervention

• Concentration of MMP-9

  Inflammatory cytokine

  1 hour post intervention

• Concentration of Cystatin C

  Inflammatory cytokine

  1 hour post intervention

• Change in Q-IPAVA

  Minute bloodflow through intrapulmonary arteriovenous anastamoses

  1 hour post intervention

Study Arms (2)

Sildenafil administration

ACTIVE COMPARATOR

Administration of 50mg sildenafil one time, one hour prior to measurements

Drug: Sildenafil

Placebo administration

PLACEBO COMPARATOR

Administration of 50mg placebo one time, one hour prior to measurements

Other: Placebo

Interventions

Sildenafil DRUG

50mg administration of sildenafil, one time, one hour prior to measurements.

Sildenafil administration

Placebo OTHER

50mg administration in gel-encapsulated microcrystalline cellulose one time, one hour prior to measurements.

Placebo administration

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Reside in geographic location near Split, Croatia
• Elite breath hold divers
• Experienced SCUBA divers

You may not qualify if:

• Previous history of coronary artery disease
• Currently taking medication or herbal supplement for any heart or respiratory disease that cannot be ceased for 48 hours prior to testing
• Women who are pregnant or trying to become pregnant
• Previous history of any condition that would prevent the subject from performing a breath hold
• Taking sildenafil or products similar to sildenafil
• Taking Nitrates or other nitric oxide donors
• Control breath hold divers can't have previous breath hold diving experience

Sponsors & Collaborators

• University of Oregon: lead

Study Sites (1)

Cardiorespiratory and Pulmonary Physiology Lab

Eugene, Oregon, 97403, United States

Location

MeSH Terms

Conditions

Foramen Ovale, Patent

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Heart Septal Defects, Atrial; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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

Study Officials

• Andrew Lovering, PhD

  University of Oregon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Utilization of placebo to mask drug administration.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Breath hold divers will be administered sildenafil and placebo. Age-matched controls will be administered sildenafil and placebo.

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 10, 2019
• Study Start: July 1, 2019
• Primary Completion: January 31, 2023
• Study Completion: July 31, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)