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Vaccination Response Modulation With a Targeted Rapamycin Protocol Study (VON TRAPP)

2026년 5월 11일 업데이트: Matthew Tunbridge, Central Adelaide Local Health Network Incorporated

Vaccination Response Modulation With a Targeted Rapamycin Protocol (VON TRAPP) Study

This study will investigate dialysis recipients' responses to important vaccines.

Research suggests that a medication commonly used by transplant recipients may improve vaccine responses. The investigators will be conducting a clinical trial to see whether a short course of low-dose Sirolimus improves the response to vaccination against respiratory syncytial virus (RSV) and influenza (flu) in patient with kidney disease over 60 years old who receive haemodialysis.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

Respiratory viruses are a significant cause of morbidity and mortality in Australia. Respiratory syncytial virus (RSV) and Influenza are major contributors to yearly respiratory virus epidemics that particularly affect older persons and persons with end-stage kidney disease.

Vaccination is available for the prevention of both RSV and Influenza, but unfortunately the conditions that confer a higher risk of morbidity and mortality with infection are also key predictors of poor responses to vaccination.

Effective vaccine responses require activation of both T and B cells to generate protective and long-lasting antibody and cellular immune responses. Immunosenescence from ageing and end-stage kidney disease, dampens antibody responses and impairs cellular immunity, rendering patients vulnerable to infection.

Previous research suggests that sirolimus(rapamycin)-based immunosuppression regimens improve vaccine immunogenicity. Sirolimus (rapamycin) is a potent inhibitor of mTORC1 which regulates memory CD8+ T cells. Targeting mTORC1 has previous been shown to improve vaccination response in humans to influenza. More recently, small studies have suggested improved responses to COVID vaccination in kidney transplant recipients switched to sirolimus (rapamycin)-based regimens.

This study will investigate a role for sirolimus (rapamycin) as a peri-vaccination immune modulation therapy. The VON TRAPP study is a phase 2a randomised clinical trial that aims to define the optimal, practical and tolerable regimen of peri-vaccination sirolimus (rapamycin) administration to positively modify vaccine responses. Haemodialysis patients over 60 years old will receive both Influenza and RSV vaccines plus either no additional treatment or a peri-vaccination regimen of sirolimus (rapamycin) to determine the most effective regimen to test further.

연구 유형

중재적

등록 (추정된)

60

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 호주
    • New South Wales
      • Camperdown, New South Wales, 호주, 2050
    • Queensland
      • Woolloongabba, Queensland, 호주, 4102
    • South Australia
      • Adelaide, South Australia, 호주, 5000
        • Royal Adelaide Hospital
        • 연락하다:

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

Inclusion Criteria:

  • End-stage kidney disease requiring in-centre haemodialysis three times per week as kidney replacement therapy
  • Aged >60 years

Exclusion Criteria:

  • Aged <60 years
  • Alternative haemodialysis regimens (e.g. twice-weekly haemodialysis, second-daily home haemodialysis)
  • Recent infection (<6 months) with proven Influenza A, Influenza B, or RSV

  • Current use of immunosuppressive medications, including:

    • Oral steroid at a dose equivalent of 5 mg/day prednisolone or greater
    • Mycophenolate mofetil
    • Azathioprine
    • Calcineurin inhibitors
    • mTOR inhibitors

  • Recent use of intravenous immunosuppressive medications (<6 months), including:

    • T-cell depleting agents (e.g. anti-thymocyte globulin)
    • B-cell depleting agents (e.g. rituximab)
    • Cyclophosphamide

  • Has a history of problems with side-effects associated with sirolimus use including

    • Angioedema
    • Active/recent opportunistic infection
    • Current or prior interstitial lung disease, non-infectious pneumonitis, organising pneumonia, or pulmonary fibrosis
    • Clinically significant pleural effusion or pericardial effusion
    • Active non-healing wounds, chronic skin ulcers, or planned major surgery/procedures
    • Current malignancy or recent malignancy with high recurrence risk
    • Severe or uncontrolled hyperlipidaemia
    • History of rhabdomyolysis
    • Severe hepatic impairment

  • Ongoing use of strong CYP3A4/P-gp inhibitors or inducers including

    • Inhibitors: Ketoconazole, Voriconazole, Itraconazole, Telithromycin, Clarithromycin
    • Inducers: Rifampicin, Rifabutin
  • Unable or unwilling to provide informed consent to participate in the trial
  • Known allergy to or intolerance of sirolimus (rapamycin) or the contents of the influenza or RSV vaccine

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 방지
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
활성 비교기: Control
Influenza and RSV vaccination without additional treatment
생물학적: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
생물학적: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
실험적: Pre-vaccine sirolimus group
Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 2 weeks after completing sirolimus course.
생물학적: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
생물학적: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
의약품: Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.
다른 이름들:
  • 라파마이신
실험적: Peri-vaccine sirolimus group
Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 1 week after commencing sirolimus course.
생물학적: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
생물학적: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
의약품: Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.
다른 이름들:
  • 라파마이신
실험적: Post-vaccine sirolimus group
Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 2 weeks prior to commencing sirolimus course.
생물학적: Influenza vaccine (Sequiris Fluad Quad)
All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad)
생물학적: RSV vaccine (Pfizer Abrysvo)
All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
의약품: Sirolimus (RAPAMUNE)
All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.
다른 이름들:
  • 라파마이신

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Vaccine-specific functional T cell memory
기간: Six weeks post vaccination
The change in functional T cell memory from baseline to six weeks post vaccine dose, measured as IFN-γ spot-forming units (SFU) by ELISpot following 18-hour stimulation of PBMCs with RSV peptides.
Six weeks post vaccination

2차 결과 측정

결과 측정
측정값 설명
기간
Cellular immune response to vaccination
기간: Six weeks post vaccination
RSV vaccine-specific cellular immunity, measured as 1) change in frequency of CD8+ RSV F protein-specific T cells from baseline to six weeks post vaccine dose, identified by flow cytometry as CD8+CD134+CD69+ following 24-hour stimulation with a protein-derived peptide array (AIM, Activation-Induced Marker assay); 2) Change in frequency of RSV F protein-specific polyfunctional T cells from baseline to six weeks post vaccine dose. Polyfunctional T cells are defined as CD4+ T cells that produce more than one of IFN-γ, IL-2 and TNF identified by flow cytometry intracellular cytokine staining following 24-hour stimulation with a protein-derived peptide array (ICS, Intracellular Cytokine Staining assay).
Six weeks post vaccination
Vaccine-specific humoral immune response
기간: Six week post vaccination
Measures of vaccine-specific humoral immunity, measured as 1) Anti-RSV F protein IgM, IgA and IgG antibody titres 6 weeks following the vaccine dose; 2) Change in haemagglutination inhibition (HAI) titre of influenza strains contained in the 2026 vaccine from baseline to six weeks post vaccination.
Six week post vaccination
Incidence of infection post-vaccination
기간: Twelve months post vaccination
Incidence of RSV or Influenza infection in the study cohort from 3 weeks post vaccination to 12-month follow-up
Twelve months post vaccination
Incidence of Sirolimus (Rapamycin) Treatment-Emergent Adverse Events [Safety and Tolerability]
기간: Six week post vaccination
Safety and tolerability of 3-week course of low-dose sirolimus (rapamycin), measured as frequency of adverse events (including serious adverse events)
Six week post vaccination
Incidence of Immunization Treatment-Emergent Adverse Events [Safety and Tolerability]
기간: Six weeks post vaccination
Safety and tolerability of vaccine regimen, assessed by 1. Frequency of adverse events following immunization (AEFI), including adverse events of special interest (AESI) such as recurrence of autoimmune disease
Six weeks post vaccination
Quality of life questionnaire
기간: Six weeks post-vaccination
Quality of life following 3-week course of low-dose sirolimus (rapamycin) and vaccination, measured with the EQ-5D-5L quality of life questionnaire. This questionnaire reports on 5 functional domains using an ordinal scale from 1 (worst) to 5 (best) to provide a combined health state score.
Six weeks post-vaccination
Circulating IL-1β analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-1β from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IFN-α2 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IFN-α2 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IFN-γ analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IFN-γ from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating TNF-α analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors TNF-α from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating MCP-1 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors MCP-1 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-6 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-6 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating CXCL8 (IL-8)
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor CXCL8 (IL-8) from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-10 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-10 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-12p70 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-12p70 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-17A analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-17A from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-18 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-18 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-23 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-23 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-33 analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-33 from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating CRP analysis
기간: Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors CRP from baseline to the end of sirolimus administration.
Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Central Adelaide Local Health Network Incorporated

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 5월 1일

기본 완료 (추정된)

2026년 7월 1일

연구 완료 (추정된)

2026년 7월 1일

연구 등록 날짜

최초 제출

2026년 5월 6일

QC 기준을 충족하는 최초 제출

2026년 5월 11일

처음 게시됨 (실제)

2026년 5월 14일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 5월 14일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 5월 11일

마지막으로 확인됨

2026년 5월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 2025/HRE00483

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Anonymized patient-level data created for the study will be available in a persistent repository upon publication. Data will be uploaded to figshare.com.

IPD 공유 기간

Anonymized IPD will be made available in a persistent repository from the date of publication of trial findings.

IPD 공유 액세스 기준

Anonymized IPD will be publicly accessible by download from the persistent repository.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다