Multilevel Models of Therapeutic Response in the Lungs

NCT02947126 | Completed Phase 1 DMC

• 2 other identifiers: PRO150703761U01HL131046-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

When developing new medications for lung diseases like Cystic Fibrosis (CF), scientists perform lab experiments using cells from the airways, physiology studies of how the lungs change when a drug is given, and clinical studies to determine how drugs affect overall health. The investigators of this study are seeking to develop computer models that will predict how patients will respond to drugs by just doing lab studies on cell samples from their noses. Such models would allow for medications to be developed more rapidly for all patients and allow treatments to be personalized as well. In order to develop these computer models a series of tests will be performed on patients who have CF. Tests will include sampling cells from the nose and measuring lung physiology using a combination of different imaging, breathing, and other studies performed both before and after participants take a therapy. Similar tests will be performed on people who do not have CF, and on the parents of the CF participants who carry a single CF gene because this will provide information on how specific genes might affect CF lung disease.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; mucociliary clearance; CFTR

Outcome Measures

Primary Outcomes (2)

• Mucociliary Clearance

  Clearance rate of Technetium sulfur colloid from the lungs

  80 minutes

• DTPA absorption rate

  DTPA absorption rate from the lungs (difference between total In-DTPA clearance rate and mucociliary clearance rate)

  80 minutes

Study Arms (4)

Cystic Fibrosis (HS, IS)

EXPERIMENTAL

CF subjects: ages 12 or older with a diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms who are clinically stable as determined by a physician co-investigator. Subjects receive HS dose on first imaging day and IS dose on the second imaging day, Indium-DTPA (1.5 mCi), Technetium sulfur colloid (8mCi), Inhaled isotonic saline (4ml), Inhaled Hypertonic Saline (4ml)

Drug: Hypertonic Saline; Drug: Isotonic Saline; Drug: Indium-DTPA; Drug: Technetium Sulfur Colloid

Cystic Fibrosis (IS, HS)

EXPERIMENTAL

CF subjects: ages 12 or older with a diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms who are clinically stable as determined by a physician co-investigator. Subjects receive IS dose on first imaging day and HS dose on the second imaging day. Indium-DTPA (1.5 mCi), Technetium sulfur colloid (8mCi), Inhaled isotonic saline (4ml), Inhaled Hypertonic Saline (4ml)

Drug: Hypertonic Saline; Drug: Isotonic Saline; Drug: Indium-DTPA; Drug: Technetium Sulfur Colloid

Parents of CF subjects

EXPERIMENTAL

Ages 18 and older, biological parent of a CF patient who is also enrolled in the study Indium-DTPA (1.5 mCi), Technetium sulfur colloid (8mCi), Inhaled isotonic saline (4ml)

Drug: Isotonic Saline; Drug: Indium-DTPA; Drug: Technetium Sulfur Colloid

non CF controls

EXPERIMENTAL

Ages 18 and older with no history of lung disease Indium-DTPA (1.5 mCi), Technetium sulfur colloid (8mCi), Inhaled isotonic saline (4ml).

Drug: Isotonic Saline; Drug: Indium-DTPA; Drug: Technetium Sulfur Colloid

Interventions

Hypertonic Saline DRUG

Inhaled 7% Hypertonic saline

Cystic Fibrosis (HS, IS); Cystic Fibrosis (IS, HS)

Isotonic Saline DRUG

Inhaled 0.9% Isotonic saline

Cystic Fibrosis (HS, IS); Cystic Fibrosis (IS, HS); Parents of CF subjects; non CF controls

Indium-DTPA DRUG

Inhaled Indium 111 DTPA

Cystic Fibrosis (HS, IS); Cystic Fibrosis (IS, HS); Parents of CF subjects; non CF controls

Technetium Sulfur Colloid DRUG

Inhaled Technetium99m sulfur colloid

Cystic Fibrosis (HS, IS); Cystic Fibrosis (IS, HS); Parents of CF subjects; non CF controls

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 12 or older
• Diagnosis of cystic fibrosis as determined by sweat test or genotype
• Clinically stable as determined by a physician co-investigator

You may not qualify if:

• Smokers or users of electronic cigarettes
• FEV1%p \<30% of predicted
• Nursing, pregnant or unwilling to test for pregnancy
• Intolerant to hypertonic saline
• Unable or unwilling to discontinue hypertonic saline, Pulmozyme, and long acting bronchodilators for 24 hrs before testing and short acting bronchodilators on testing days.
• Ages 18 and older
• Biological parent of a CF patient who is also enrolled in the study
• Smokers or users of electronic cigarettes
• FEV1%p \<30% of predicted
• Nursing, pregnant or unwilling to test for pregnancy
• Unwilling to discontinue long acting bronchodilators for 24 hrs before testing and short acting bronchodilators on testing days.
• Unwilling to perform CFTR genotyping.
• Ages 18 and older
• No history of lung disease
• Smokers or users of electronic cigarettes

Sponsors & Collaborators

• Tim Corcoran: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Links

• Publication describing outcomes

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Saline Solution, Hypertonic; Sodium Chloride; Pentetic Acid; Technetium Tc 99m Sulfur Colloid

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Sulfur Compounds; Technetium Compounds

Study Officials

• Tim Corcoran, Ph.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: October 27, 2016
• Study Start: January 1, 2017
• Primary Completion: February 1, 2020
• Study Completion: December 1, 2022
• Last Updated: January 13, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)