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BEGIN Novel ImagiNG Biomarkers (BEGINNING)

Primary Purpose

Cystic Fibrosis

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

129Xe

About this trial

This is an interventional diagnostic trial for Cystic Fibrosis

Eligibility Criteria

6 Years - 8 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent (and assent where appropriate) obtained from the subject or subject's legal representative.
Willingness to adhere to the study-visit schedule and other protocol requirements.
Ages 6-8 years old at baseline MRI visit (may be enrolled up to 60 days before 6th birthday).
Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
1. Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine iontophoresis test
2. Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Physician intent to prescribe triple-combination therapy
Clinically-stable with no respiratory tract infection at the time of enrollment.
No change in chronic maintenance therapies in the 28 days prior to enrollment.
Ability to cooperate with MRI procedures

Exclusion Criteria:

Individuals currently on ivacaftor therapy (including Kalydeco, Orkambi, and Symdeko) and with at least one gating mutation. Gating mutations include G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D.
Acute respiratory symptoms (e.g. wheezing) at the time of the MRI.
Acute respiratory infection, defined as increased cough, wheezing or respiratory rate in the 28 days prior to enrollment.
Chronic lung disease not related to CF
Chronic liver disease not related to CF
Acute pancreatitis, defined by clinical criteria (45).
Chronic pancreatic disease not related to CF.
Physical findings that would compromise the safety of the subject or the quality of the study data as determined at the discretion of the site investigator.
Any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Sites / Locations

University of Kansas Medical Center
Carrie Stevens
University of VirginiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Pre Trikafta

Post Trikafta

Arm Description

129Xe MRI

Outcomes

Primary Outcome Measures

Ventilation Defect Percentage change from baseline

For pulmonary MRI, the primary outcome measure is the change in 129Xe ventilation defect percentage (VDP) from pre-therapy baseline to the one-year follow-up visit.

Pancreas volume

For pancreatic MRI, the primary outcome measure is change in pancreas volume normalized to BSA between pre-therapy baseline and one-year follow-up visit.

Secondary Outcome Measures

Abdominal T1 values

Changes in MRI T1 average in the liver and pancreas, from baseline to follow up at 1 year

Lung reader score

Changes in reader score for visible structural defects from proton MRI, from baseline to follow up at 1 year

Full Information

NCT ID

NCT05517655

First Posted

April 6, 2022

Last Updated

October 23, 2023

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

University of Kansas, University of Iowa, University of Virginia

1. Study Identification

Unique Protocol Identification Number

NCT05517655

Brief Title

BEGIN Novel ImagiNG Biomarkers

Acronym

BEGINNING

Official Title

BEGIN Novel ImagiNG Biomarkers

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 1, 2022 (Actual)

Primary Completion Date

November 1, 2028 (Anticipated)

Study Completion Date

November 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

University of Kansas, University of Iowa, University of Virginia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

To determine the treatment effect of triple-combination therapy in 6-8 year olds after presumed FDA approval, using rapid structural and functional pulmonary and abdominal MRI (UTE and 129Xe).

Detailed Description

The overall hypothesis is that multi-organ MRI will provide more sensitive, robust outcome measures in young CF patients than traditional measures employed in the BEGIN study and that these novel measures will be more sensitive to treatment effects, tested here by comparison before and after triple-combination modulator therapy. By understanding the nature of early lung obstruction and characteristic changes in the liver and pancreas over time, we continue to lay the groundwork for more personalized medicine in the future. Assessing treatment response and clinical benefit in children with CF who are clinically normal per standard outcomes (e.g., spirometry, pancreatic function) will become paramount as triplecombination therapy is extended to younger patients with milder CF clinical presentation than their historic peers. Here the sensitivity and profile free of ionizing-radiation exposure of MRI can be leveraged to follow an individual with CF over time to quantify changes with therapy-with additional spatial resolution unavailable from standard clinical testing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

Outcomes Assessor

Allocation

Non-Randomized

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pre Trikafta

Arm Type

Experimental

Arm Description

129Xe MRI

Arm Title

Post Trikafta

Arm Type

Experimental

Arm Description

129Xe MRI

Intervention Type

Drug

Intervention Name(s)

129Xe

Intervention Description

Rapid spatial mapping of lung, liver, and pancreatic structure and function is now possible with a combination of hyperpolarized 129Xe and traditional proton MRI, all absent sedation and ionizing radiation.

Primary Outcome Measure Information:

Title

Ventilation Defect Percentage change from baseline

Description

For pulmonary MRI, the primary outcome measure is the change in 129Xe ventilation defect percentage (VDP) from pre-therapy baseline to the one-year follow-up visit.

Time Frame

1 year

Title

Pancreas volume

Description

For pancreatic MRI, the primary outcome measure is change in pancreas volume normalized to BSA between pre-therapy baseline and one-year follow-up visit.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Abdominal T1 values

Description

Changes in MRI T1 average in the liver and pancreas, from baseline to follow up at 1 year

Time Frame

1 year

Title

Lung reader score

Description

Changes in reader score for visible structural defects from proton MRI, from baseline to follow up at 1 year

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

8 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent (and assent where appropriate) obtained from the subject or subject's legal representative. Willingness to adhere to the study-visit schedule and other protocol requirements. Ages 6-8 years old at baseline MRI visit (may be enrolled up to 60 days before 6th birthday). Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria: Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine iontophoresis test Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene Physician intent to prescribe triple-combination therapy Clinically-stable with no respiratory tract infection at the time of enrollment. No change in chronic maintenance therapies in the 28 days prior to enrollment. Ability to cooperate with MRI procedures Exclusion Criteria: Individuals currently on ivacaftor therapy (including Kalydeco, Orkambi, and Symdeko) and with at least one gating mutation. Gating mutations include G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D. Acute respiratory symptoms (e.g. wheezing) at the time of the MRI. Acute respiratory infection, defined as increased cough, wheezing or respiratory rate in the 28 days prior to enrollment. Chronic lung disease not related to CF Chronic liver disease not related to CF Acute pancreatitis, defined by clinical criteria (45). Chronic pancreatic disease not related to CF. Physical findings that would compromise the safety of the subject or the quality of the study data as determined at the discretion of the site investigator. Any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Carrie Stevens, BS

Phone

(513) 636-9973

carrie.stevens@cchmc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Penny New, BS

Phone

(513) 636-9973

Penny.New@cchmc.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jason Woods, PhD

Organizational Affiliation

Children's Hospital Medical Center, Cincinnati

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

Carrie Stevens

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

University of Virginia

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22903

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jamie Mata

First Name & Middle Initial & Last Name & Degree

Jamie Mata

First Name & Middle Initial & Last Name & Degree

Deborah Froh

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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