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A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT) (PROSPECT)

2020年5月12日 更新者：Steven M Rowe、University of Alabama at Birmingham
identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF

調査の概要

状態

完了

条件

介入・治療

詳細な説明

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Over 1,900 mutations, categorized into five genotypic or functional classes are implicated in causing CF. Severity of disease varies widely in CF based on CFTR-dependent and independent factors. Progressive obstructive lung disease is the main determinant of morbidity and mortality in CF; therefore it is critical to identify biomarker profiles that reflect and predict this phenotypic variability, and understand their relationship to residual CFTR activity. Emerging CFTR modulator therapies that directly target defective CFTR are being evaluated in pivotal clinical trials and may become available in the next few years. It is not known how partial restoration of CFTR function might impact CF disease progression and disease-related biomarkers. Thus there is urgent need to i) identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF

研究の種類

観察的

入学 (実際)

452

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • Alabama
      • Birmingham、Alabama、アメリカ、35233
        • University of Alabama at Birmingham
    • California
      • Los Angeles、California、アメリカ、90027
        • Childrens Hospital Los Angeles
      • Palo Alto、California、アメリカ、94394
        • Lucile S. Packard Children's Hospital
    • Colorado
      • Aurora、Colorado、アメリカ、80045
        • The Children's Hospital Colarado
      • Denver、Colorado、アメリカ、80206
        • National Jewish Health
    • Illinois
      • Chicago、Illinois、アメリカ、60611-2605
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis、Indiana、アメリカ
        • Indianapolis University Hospital; James Whitcomb Riley Hospital for Children
    • Kansas
      • Kansas City、Kansas、アメリカ、66160
        • The University of Kansas Hospital
    • Maryland
      • Baltimore、Maryland、アメリカ、21287
        • John Hopkins University
    • Massachusetts
      • Boston、Massachusetts、アメリカ、02114
        • Massachusetts General Hospital
      • Boston、Massachusetts、アメリカ、02115
        • Children's Hospital Boston
    • Michigan
      • Detroit、Michigan、アメリカ、48201
        • Children's Hospital of Michigan
      • Grand Rapids、Michigan、アメリカ、49503
        • Devon Children's Hospital at Spectrum Health
    • Minnesota
      • Minneapolis、Minnesota、アメリカ、55455
        • University of Minnesota
    • Missouri
      • Kansas City、Missouri、アメリカ、64108
        • Children's Mercy Hospital
      • Saint Louis、Missouri、アメリカ、63104
        • Cardinal Glennon Children's Medical Center
      • Saint Louis、Missouri、アメリカ
        • St. Louis Children's Hospital
    • New Hampshire
      • Lebanon、New Hampshire、アメリカ
        • Dartmouth Hitchcock Medical Center
    • New York
      • Buffalo、New York、アメリカ、14222
        • Women and Children's Hospital of Buffalo
      • New York、New York、アメリカ、10032
        • Columbia University Medical Center
      • Valhalla、New York、アメリカ、10595
        • Maria Fareri Children's Hospital; Westchester Medical Center
    • North Carolina
      • Chapel Hill、North Carolina、アメリカ、27599
        • University of North Carolina at Chapel Hill
    • Ohio
      • Akron、Ohio、アメリカ、44308
        • Akron Children's Hospital
      • Cincinnati、Ohio、アメリカ、45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland、Ohio、アメリカ、44106
        • University Hospital of Cleveland
      • Columbus、Ohio、アメリカ
        • Nation Wide Childrens Hospital
    • Oregon
      • Portland、Oregon、アメリカ、97239
        • Oregon Health & Sciences University
    • Pennsylvania
      • Hershey、Pennsylvania、アメリカ、17033
        • Hershey Medical Center; Penn State Children's Hospital
      • Philadelphia、Pennsylvania、アメリカ
        • Children's Hospital of Philadelphia
      • Pittsburgh、Pennsylvania、アメリカ、15213
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Charleston、South Carolina、アメリカ、29403
        • Medical University of South Carolina
    • Tennessee
      • Nashville、Tennessee、アメリカ、37232-9500
        • The Children's Hospital at Vanderbilt
    • Texas
      • Houston、Texas、アメリカ、77030
        • Baylor College of Medicine/Texas Children's Hospital
    • Utah
      • Salt Lake City、Utah、アメリカ、84132
        • Primary Children's Hospital
    • Washington
      • Seattle、Washington、アメリカ、98195
        • University of Washington Medical Center
      • Seattle、Washington、アメリカ、98145-9807
        • Seattle Children's Hospital
    • Wisconsin
      • Milwaukee、Wisconsin、アメリカ、53226
        • Froedtert Hospital
      • Milwaukee、Wisconsin、アメリカ、55455
        • Children's Hospital of Wisconsin

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

12年歳以上 (子、大人、高齢者)

健康ボランティアの受け入れ

はい

受講資格のある性別

全て

サンプリング方法

確率サンプル

調査対象母集団

Part A N = 260 (210 CF, 50 non-CF controls)

  • Cohort 1: 50 non-CF control subjects ≥ 12 years of age, with at least 15 subjects 12 - 21 yrs of age
  • Cohort 2: 50 Partial CFTR Function CF subjects with at least one class IV/V CFTR mutation, ≥ 12 years of age
  • Cohort 3 160 Absent CFTR Function CF subjects with two class I/II mutations ≥ 12 years of age

Part B

Up to 250 CF subjects who are homozygous for F508del mutation and who are prescribed ivacaftor/lumacafor for clinical care will be allowed to enroll. This will include :

  • Cohort 3 subjects homozygous for F508del mutation from Part A who are prescribed ivacaftor/lumacaftor will be invited to participate in Part B (up to 100 potential subjects).
  • Up to 150 additional CF subjects homozygous for F508del mutation ≥ 12 years of age who did not participate in Part A but are otherwise eligible for participation in Part B.

説明

Inclusion Criteria Part A COHORT 1:

  • 1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.

    2. Be willing and able to adhere to the study visit schedule and other protocol requirements 3. Male or female ≥ 12 years of age at Visit 1. 4. Have a body mass index (BMI) of:

    • For subjects ≥ 18 years of age: ≤ 30 kg/m2

    • For subjects 12 - 17 years of age: ≤ 95th percentile 5. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.

      6. To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study.

Inclusion Cohorts 2-3

  1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
  2. Male or female ≥ 12 years of age at Visit 1.

  3. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and the following criteria: Cohort 2: (Partial Function CFTR CF)

    • Two mutations in the CFTR gene:

      • At least one allele must be a Class IV or V mutation
      • The second allele can be within any CFTR mutation class.
    • Pancreatic sufficient (based on the absence of daily PERT use)
    • At least one historic sweat chloride ≥60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) OR sweat chloride results ≥ 40, but < 60mEQ/L upon permission of the PROSPECT Investigator-Sponsors.

    Cohort 3: (Absent Function CF)

    • Two class I or II CFTR mutations

  4. Enrolled in the Cystic Fibrosis Foundation Patient Registry. Patients may enroll in the Registry at Visit 1 if not previously enrolled.
  5. Clinically stable with no significant changes in health status within 2 weeks prior to Visit 1.
  6. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.
  7. To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study

Part B Inclusion

  1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
  2. Physician decision to treat with ivacaftor/lumacaftor.
  3. Completion of at least Visit 1 and Visit 2 of Part A

Exclusion Criteria PART A COHORT 1

  1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  2. A history of any clinically significant medical illness or medical disorder that requires ongoing systemic medical therapy, including (but not limited to) cardiovascular disease, neuromuscular disease, hematological disease including bleeding disorders, chronic respiratory disease (including persistent asthma), hepatic or gastrointestinal (GI) disease, neurological disease, neoplastic disease, renal diseases, or endocrine disorders including diabetes.
  3. Acute illness requiring any new prescription or over-the-counter treatment within 14 days prior to Visit 1.
  4. Major or traumatic surgery within 12 weeks prior to Visit 1.
  5. For females of child-bearing potential: a positive pregnancy test at Visit 1.
  6. Initiation of any new chronic therapy within 28 days prior to Visit 1.
  7. Use of an investigational agent within 28 days prior to Visit 1.

Exclusion Part A COHORTS 2-3

  1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  2. Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 1.
  3. Major or traumatic surgery within 12 weeks prior to Visit 1.
  4. For females of child-bearing potential: a positive pregnancy test at Visit 1.
  5. Initiation of any new chronic therapy (e.g., ibuprofen Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 1.
  6. Use of an investigational agent within 28 days prior to Visit 1.
  7. Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for > 12 weeks prior to visit 1).
  8. Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).
  9. Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 1.
  10. History of lung or liver transplantation, or listing for organ transplantation.

Exclusion PART B

  1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  2. Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 4.
  3. Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 4.
  4. Use of an investigational agent within 28 days prior to Visit 4.
  5. Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for > 12 weeks prior to Visit 4).
  6. Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).
  7. Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 4.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

コホートと介入

グループ/コホート
介入・治療
Part A
  • Cohort 1: Healthy Controls
  • Cohort 2: Partial CFTR function CF (class IV/V)
  • Cohort 3: Absent CFTR function CF (Class I/II)
他の：観察的
Part B
CF patients who are homozygous for the F508del
他の：観察的

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Sweat Chloride by Cohort (Part A Only)
時間枠：For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.

This is the primary endpoint for Part A per the PROSPECT protocol. Mean sweat chloride was not reported for Part B, as it is not a relevant statistic.

For cohort 1, sweat chloride is from day 0 only. For cohorts 2-3, sweat chloride was averaged from days 0, 14, 90 via a random intercept longitudinal model.
For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.
6 Month Change in FEV1 Percent Predicted (Part B Only)
時間枠：Baseline and 6 months
This is the primary endpoint for Part B per the PROSPECT protocol. Change in FEV1 Percent Predicted is only relevant for Part B as it captures changes in lung function post-initiation of Ivacaftor/Lumacaftor.
Baseline and 6 months

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University of Alabama at Birmingham

協力者

Cystic Fibrosis Foundation

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2015年3月1日

一次修了 (実際)

2018年4月25日

研究の完了 (実際)

2018年7月27日

試験登録日

最初に提出

2015年5月22日

QC基準を満たした最初の提出物

2015年6月19日

最初の投稿 (見積もり)

2015年6月22日

学習記録の更新

投稿された最後の更新 (実際)

2020年5月20日

QC基準を満たした最後の更新が送信されました

2020年5月12日

最終確認日

2020年5月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

  • PROSPECT

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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