Next Generation Sequencing to Detect Acute Rejection in Lung Transplant Patients.

NCT05260372 | Unknown

• 1 other identifier: 1883/2018
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Lung transplantation is a consolidated treatment in selected patients with end-stage respiratory diseases; however, acute rejection remains an important cause of lung allograft loss and a risk factor for chronic allograft dysfunction. Histopathological examination of lung tissue is the gold standard for the diagnosis of acute rejection, therefore recipients undergo surveillance transbronchial biopsy and bronchoalveolar lavage after transplantation. However, the obtained tissue is sometimes inadequate for histopathology, and the endoscopic procedure can lead to complications (bleeding, pneumothorax). The quantification of donor-derived cell-free DNA (ddcfDNA) in the recipient plasma has shown to be increased in case of acute rejection, and could represent an early and non-invasive diagnostic marker to detect acute rejection. We planned to enroll all patients aged 18 to 65 years old enlisted for lung transplantation at our centre. Patients undergoing retransplantation and patients with a history of prior solid organ transplantation were excluded. The quantification of donor-derived cell-free DNA was performed 15 days and 3, 6, and 12 months after transplantation, concurrently with the routine surveillance bronchoscopies as per our protocol; the same analysis was also conducted in case of suspected clinical rejection.

Conditions

Lung Transplant Rejection

Keywords

Acute rejection; Donor-derived cell-free DNA; Lung transplantation; Next-generation sequencing

Outcome Measures

Primary Outcomes (1)

• Proportion ddcfDNA

  Proportion of the ddcfDNA on the recipient's plasma cell free DNA

  1 year

Secondary Outcomes (1)

• ddcfDNA-clinical data correlation

  1 year

Study Arms (1)

Lung transplantation recipients

Recipients aged 18 to 65 years old undergoing lung transplantation at Fondazione IRCCS Ospedale Policlinico Milano undergoing quantification of donor-derived cell-free DNA on serial plasma samples

Diagnostic Test: Quantification of donor-derived cell-free DNA

Interventions

Quantification of donor-derived cell-free DNA DIAGNOSTIC_TEST

Quantification of ddcfDNA on serial plasma samples during follow-up after lung transplantation

Lung transplantation recipients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing lung transplantation at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

You may qualify if:

• Patients undergoing lung transplantation at our centre
• Patients aged 18 to 65 years old
• Written informed consent to partecipate in the study

You may not qualify if:

• Patients undergoing retransplantation
• Patients with a history of prior solid organ transplantation

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• University of Milan: collaborator

Study Sites (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Related Publications (13)

• Report CRT, Italy, Rete nazionale trapianti, 2017

  BACKGROUND

• Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, Levvey BJ, Lund LH, Meiser B, Rossano JW, Stehlik J; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time. J Heart Lung Transplant. 2017 Oct;36(10):1047-1059. doi: 10.1016/j.healun.2017.07.016. Epub 2017 Jul 19. No abstract available.

  PMID: 28784324 BACKGROUND

• Lande JD, Patil J, Li N, Berryman TR, King RA, Hertz MI. Novel insights into lung transplant rejection by microarray analysis. Proc Am Thorac Soc. 2007 Jan;4(1):44-51. doi: 10.1513/pats.200605-110JG.

  PMID: 17202291 BACKGROUND

• Tosi D, Carrinola R, Morlacchi LC, Tarsia P, Rossetti V, Mendogni P, Rosso L, Righi I, Damarco F, Nosotti M. Surveillance Transbronchial Biopsy Program to Evaluate Acute Rejection After Lung Transplantation: A Single Institution Experience. Transplant Proc. 2019 Jan-Feb;51(1):198-201. doi: 10.1016/j.transproceed.2018.04.073. Epub 2018 Jun 28.

  PMID: 30655138 BACKGROUND

• Rademacher J, Suhling H, Greer M, Haverich A, Welte T, Warnecke G, Gottlieb J. Safety and efficacy of outpatient bronchoscopy in lung transplant recipients - a single centre analysis of 3,197 procedures. Transplant Res. 2014 May 27;3:11. doi: 10.1186/2047-1440-3-11. eCollection 2014.

  PMID: 24917927 BACKGROUND

• De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Nicolls MR, Cornfield D, Weill D, Valantine H, Khush KK, Quake SR. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41. doi: 10.1073/pnas.1517494112. Epub 2015 Oct 12.

  PMID: 26460048 BACKGROUND

• Agbor-Enoh S, Jackson AM, Tunc I, Berry GJ, Cochrane A, Grimm D, Davis A, Shah P, Brown AW, Wang Y, Timofte I, Shah P, Gorham S, Wylie J, Goodwin N, Jang MK, Marishta A, Bhatti K, Fideli U, Yang Y, Luikart H, Cao Z, Pirooznia M, Zhu J, Marboe C, Iacono A, Nathan SD, Orens J, Valantine HA, Khush K. Late manifestation of alloantibody-associated injury and clinical pulmonary antibody-mediated rejection: Evidence from cell-free DNA analysis. J Heart Lung Transplant. 2018 Jul;37(7):925-932. doi: 10.1016/j.healun.2018.01.1305. Epub 2018 Jan 31.

  PMID: 29500138 BACKGROUND

• De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.

  PMID: 24944192 BACKGROUND

• Rizopoulos, D. Joint Models for Longitudinal and Time-to-Event Data, with Applications in R. Boca Raton: Chapman & Hall/CRC. 2012.

  BACKGROUND

• Wu, L. Mixed Effects Models for Complex Data. Boca Raton: Chapman & Hall/CRC, Chapter 8. 2009

  BACKGROUND

• Rizopoulos, D. The R package JMbayes for fitting joint models for longitudinal and timeto-event data using MCMC. Journal of Statistical Software 72(7), 1-45. doi:10.18637/jss.v072.i07. 2016

  BACKGROUND

• Rizopoulos D. Dynamic predictions and prospective accuracy in joint models for longitudinal and time-to-event data. Biometrics. 2011 Sep;67(3):819-29. doi: 10.1111/j.1541-0420.2010.01546.x. Epub 2011 Feb 9.

  PMID: 21306352 BACKGROUND

• R Foundation for Statistical Computing, Vienna, Austria(2015)

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, Lung biopsy, Bronchoalveolar lavage

Study Officials

• Mario Nosotti, MD, Professor

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor, Chief of Thoracic Surgery and Lung transplantation Unit

Study Record Dates

• First Submitted: February 19, 2022
• First Posted: March 2, 2022
• Study Start: October 4, 2018
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 2, 2022

Record last verified: 2022-02

Locations

IT (1)