Immune Markers in Pediatric ITP on Second Line Therapy

NCT ID: NCT06093529

Last Updated: 2023-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

42 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-01-01

Study Completion Date

2025-02-01

Brief Summary

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Immune thrombocytopenia (ITP) is a common autoimmune disease characterized by low platelet count and increased risk of bleeding. It affects approximately 50 to 100 cases per million people per year, with children accounting for half of the cases.

Detailed Description

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Antiplatelet factors in the plasma of ITP patients, specifically IgG, have been attributed to platelet destruction through phagocytosis or complement-mediated lysis. However, these antibodies are only present in 60-70% of ITP patients, suggesting that other mechanisms may be involved in platelet destruction.

B lymphocytes play a critical role in immune responses through antibody production, antigen presentation to T cells, and cytokine secretion. CD4+ T helper cells play a crucial role in supporting B cell development into antibody-secreting plasma cells. Furthermore, evidence of auto reactive CD4+ T cells targeting platelet epitopes has been reported.

It was found that there is clonal expansion of a particular subset of CD8+ T cells, known as terminally differentiated effector memory T cells (TEMRA cells), in refractory ITP. Furthermore, CD8+ T cells induce platelet activation and apoptosis in an antibody-independent mechanism for refractory thrombocytopenia that may be amenable to therapeutic targeting. IFN-γ is an important cytokine involved in host defence and immune regulation. It is primarily produced by T helper, cytotoxic T, and natural killer cells. Dysregulated secretion of IFN-γ has been implicated in the development of autoimmune disorders. Initial studies on ITP focused on the role of autoantibodies. Therefore, drug discovery efforts have focused on suppressing aberrant humoral immunity through B cell depletion, disruption of immunoreceptor, and inhibition of autoantibody activity. By comparing the marker expression in different treatment response groups, the investigator can potentially identify markers that may serve as predictive or prognostic indicators of treatment response. This information could be valuable for guiding treatment decisions and optimizing patient outcomes in pediatric ITP.

Conditions

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ITP - Immune Thrombocytopenia

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Respondents to second-line therapy

Immune markers in ITPpatients Respondant to second line therapy

complete blood count, CD3+ , CD4+ , CD8+, CD16+, CD56+, IFN-γ.

Intervention Type DIAGNOSTIC_TEST

1. Full history
2. Thorough clinical examinations
3. Laboratory investigations will include:

1. complete blood count with focus on platelet count, platelet distribution width and mean platelet volume. Platelet count will be confirmed by direct blood film and blood smear.
2. Measurements of CD3+, CD4+, CD8+ and natural killer cells (CD16+, CD56+) will be conducted using flow cytometry.
3. Serum IFN-γ levels will be determined using an ELISA kit.
4. Response to the treatment will be assessed according to The International Working Group criteria which defines Response as platelet count ≥ 30 x 10⁹/L and \>2-fold increase in platelet count from baseline and absence of bleeding, measured on 2 occasions greater than 7 days apart. No response is characterized by a platelet count \<30 x 10⁹/L or a less than 2-fold increase in platelet count from baseline, or the presence of bleeding.

Non-Respondents to second-line therapy

Immune markers in ITPpatients nonrespondant to second line therapy

complete blood count, CD3+ , CD4+ , CD8+, CD16+, CD56+, IFN-γ.

Intervention Type DIAGNOSTIC_TEST

1. Full history
2. Thorough clinical examinations
3. Laboratory investigations will include:

1. complete blood count with focus on platelet count, platelet distribution width and mean platelet volume. Platelet count will be confirmed by direct blood film and blood smear.
2. Measurements of CD3+, CD4+, CD8+ and natural killer cells (CD16+, CD56+) will be conducted using flow cytometry.
3. Serum IFN-γ levels will be determined using an ELISA kit.
4. Response to the treatment will be assessed according to The International Working Group criteria which defines Response as platelet count ≥ 30 x 10⁹/L and \>2-fold increase in platelet count from baseline and absence of bleeding, measured on 2 occasions greater than 7 days apart. No response is characterized by a platelet count \<30 x 10⁹/L or a less than 2-fold increase in platelet count from baseline, or the presence of bleeding.

Interventions

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complete blood count, CD3+ , CD4+ , CD8+, CD16+, CD56+, IFN-γ.

1. Full history
2. Thorough clinical examinations
3. Laboratory investigations will include:

1. complete blood count with focus on platelet count, platelet distribution width and mean platelet volume. Platelet count will be confirmed by direct blood film and blood smear.
2. Measurements of CD3+, CD4+, CD8+ and natural killer cells (CD16+, CD56+) will be conducted using flow cytometry.
3. Serum IFN-γ levels will be determined using an ELISA kit.
4. Response to the treatment will be assessed according to The International Working Group criteria which defines Response as platelet count ≥ 30 x 10⁹/L and \>2-fold increase in platelet count from baseline and absence of bleeding, measured on 2 occasions greater than 7 days apart. No response is characterized by a platelet count \<30 x 10⁹/L or a less than 2-fold increase in platelet count from baseline, or the presence of bleeding.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Pediatric patients diagnosed with immune thrombocytopenia who are undergoing second line therapy with either eltrombopag or romiplostim.

Exclusion Criteria

* Include acute immune thrombocytopenic children receiving first line therapy and those with secondary immune thrombocytopenia.
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Gehad Mahmoud Abdelsalam

Principle Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Khaled I El-sayeh, M.D.

Role: STUDY_DIRECTOR

Assiut University

Mostafa M Embaby, M.D.

Role: STUDY_DIRECTOR

Assiut University

Azhar A Mohammed, M.D.

Role: STUDY_DIRECTOR

Assiut University

Central Contacts

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Gehad M Abdelsalam, M.Sc.

Role: CONTACT

+201091294596

References

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Kayal L, Jayachandran S, Singh K. Idiopathic thrombocytopenic purpura. Contemp Clin Dent. 2014 Jul;5(3):410-4. doi: 10.4103/0976-237X.137976.

Reference Type BACKGROUND
PMID: 25191085 (View on PubMed)

Zufferey A, Kapur R, Semple JW. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J Clin Med. 2017 Feb 9;6(2):16. doi: 10.3390/jcm6020016.

Reference Type BACKGROUND
PMID: 28208757 (View on PubMed)

Cancro MP. The BLyS/BAFF family of ligands and receptors: key targets in the therapy and understanding of autoimmunity. Ann Rheum Dis. 2006 Nov;65 Suppl 3(Suppl 3):iii34-6. doi: 10.1136/ard.2006.058412.

Reference Type BACKGROUND
PMID: 17038469 (View on PubMed)

Kuwana M, Kaburaki J, Kitasato H, Kato M, Kawai S, Kawakami Y, Ikeda Y. Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura. Blood. 2001 Jul 1;98(1):130-9. doi: 10.1182/blood.v98.1.130.

Reference Type BACKGROUND
PMID: 11418472 (View on PubMed)

Malik A, Sayed AA, Han P, Tan MMH, Watt E, Constantinescu-Bercu A, Cocker ATH, Khoder A, Saputil RC, Thorley E, Teklemichael A, Ding Y, Hart ACJ, Zhang H, Mitchell WA, Imami N, Crawley JTB, Salles-Crawley II, Bussel JB, Zehnder JL, Adams S, Zhang BM, Cooper N. The role of CD8+ T-cell clones in immune thrombocytopenia. Blood. 2023 May 18;141(20):2417-2429. doi: 10.1182/blood.2022018380.

Reference Type BACKGROUND
PMID: 36749920 (View on PubMed)

Pollard KM, Cauvi DM, Toomey CB, Morris KV, Kono DH. Interferon-gamma and systemic autoimmunity. Discov Med. 2013 Sep;16(87):123-31.

Reference Type BACKGROUND
PMID: 23998448 (View on PubMed)

HARRINGTON WJ, MINNICH V, HOLLINGSWORTH JW, MOORE CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951 Jul;38(1):1-10. No abstract available.

Reference Type BACKGROUND
PMID: 14850832 (View on PubMed)

Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci. 1965 Jun 30;124(2):499-542. doi: 10.1111/j.1749-6632.1965.tb18984.x. No abstract available.

Reference Type BACKGROUND
PMID: 5214832 (View on PubMed)

van Leeuwen EF, van der Ven JT, Engelfriet CP, von dem Borne AE. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood. 1982 Jan;59(1):23-6.

Reference Type BACKGROUND
PMID: 7032627 (View on PubMed)

Ghanima W, Khelif A, Waage A, Michel M, Tjonnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. doi: 10.1016/S0140-6736(14)61495-1. Epub 2015 Feb 5.

Reference Type BACKGROUND
PMID: 25662413 (View on PubMed)

Mahevas M, Azzaoui I, Crickx E, Canoui-Poitrine F, Gobert D, Languille L, Limal N, Guillaud C, Croisille L, Jeljeli M, Batteux F, Baloul S, Fain O, Pirenne F, Weill JC, Reynaud CA, Godeau B, Michel M. Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial. Haematologica. 2021 Sep 1;106(9):2449-2457. doi: 10.3324/haematol.2020.259481.

Reference Type BACKGROUND
PMID: 32817288 (View on PubMed)

Newland AC, Sanchez-Gonzalez B, Rejto L, Egyed M, Romanyuk N, Godar M, Verschueren K, Gandini D, Ulrichts P, Beauchamp J, Dreier T, Ward ES, Michel M, Liebman HA, de Haard H, Leupin N, Kuter DJ. Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. Am J Hematol. 2020 Feb;95(2):178-187. doi: 10.1002/ajh.25680. Epub 2019 Dec 10.

Reference Type BACKGROUND
PMID: 31821591 (View on PubMed)

Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.

Reference Type BACKGROUND
PMID: 17695343 (View on PubMed)

Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.

Reference Type BACKGROUND
PMID: 19005182 (View on PubMed)

Other Identifiers

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ITPIMMUNEMARKERS

Identifier Type: -

Identifier Source: org_study_id

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