Ignite Creation Date:
2024-05-06 @ 5:06 PM
Last Modification Date:
2024-10-26 @ 2:22 PM
Study NCT ID:
NCT05190627
Status:
UNKNOWN
Last Update Posted:
2022-01-27
First Post:
2021-12-11
Brief Title:
Effect of Loratadine in Lymphangioleiomyomatosis
Sponsor:
Institut dInvestigació Biomèdica de Bellvitge
Organization:
Institut dInvestigació Biomèdica de Bellvitge
Study Overview
Official Title:
Phase II Clinical Trial Evaluating the Effect of Loratadine Associated to Rapamicyn in Patients With Lymphangioleiomyomatosis
Status:
UNKNOWN
Status Verified Date:
2022-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LORALAM
Brief Summary:
INTRODUCTION LAM is a rare and lethal disease characterized by progressive cystic lung destruction Inhibition of mTOR with rapamycin is the current standard of care SOC which can slow-down disease Plasma major histamine metabolite Methylimidazoleacetic acid MIAA is increased in LAM Loratadine is a histamine receptor antagonist HR1 which inhibits LAM cell proliferation Therefore a novel phase-II clinical trial for assessing safety and potential benefits of loratadine in LAM has been initiated
METHODS LORALAM clinical trial phase-II double-blind randomized placebo controlled parallel-group multicentre study initiates recruitment in July 2020 Enrollment plan includes 62 subjects with LAM on treatment with rapamycin 3 months randomized 11 to add oral loratadine 10mgday or placebo once daily for 52 weeks Recruitment will end in June 2021 The primary endpoints are 1 to assess the safety profile of loratadine associated with rapamycin 2 lung function decline after 52 weeks of treatment The secondary endpoints are a quality of life and progression free-survival time b changes in the established LAM serum biomarker VEGFD c the utility of MIAA for monitoring disease progression and biological treatment effect
ETHICS AND DISSEMINATION The study will be carried out in accordance with Good Clinical Practice guidelines Declaration of Helsinki principles and each ethical committee This clinical trial contemplates the possibility of increasing the number of centers and including patients from patient support groups LAM foundation AELAM
METHODS LORALAM clinical trial phase-II double-blind randomized placebo controlled parallel-group multicentre study initiates recruitment in July 2020 Enrollment plan includes 62 subjects with LAM on treatment with rapamycin 3 months randomized 11 to add oral loratadine 10mgday or placebo once daily for 52 weeks Recruitment will end in June 2021 The primary endpoints are 1 to assess the safety profile of loratadine associated with rapamycin 2 lung function decline after 52 weeks of treatment The secondary endpoints are a quality of life and progression free-survival time b changes in the established LAM serum biomarker VEGFD c the utility of MIAA for monitoring disease progression and biological treatment effect
ETHICS AND DISSEMINATION The study will be carried out in accordance with Good Clinical Practice guidelines Declaration of Helsinki principles and each ethical committee This clinical trial contemplates the possibility of increasing the number of centers and including patients from patient support groups LAM foundation AELAM
Detailed Description:
Lymphangioleiomyomatosis LAM is a rare and lethal lung disease affecting almost exclusively women of childbearing age and characterized by progressive cystic lung destruction LAM results from germline and somatic loss-of-function mutations in the tuberous sclerosis complex 1 and 2 genes TSC12 and therefore diseased cells show abnormal activation of the mechanistic target of rapamycin mTOR Inhibition of mTOR with rapamycin also known as sirolimus is the current standard of care However this therapy does not fully kill LAM cells shows variable tolerability and treatment answer Therefore sirolimus has slowed-down disease progression but young patients still need lung transplantation despite treatment In addition LAM diagnosis and clinical monitoring is also challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests Here guided by comprehensive preclinical data obtained in the context of a Spanish research network for LAM and with the support of the national Association of LAM patients AELAM the investigators propose a phase-II clinical trial for assessing if the tricyclic antihistamine loratadine is effective in slowing the progression of lung disease in LAM Loratadine is an histamine receptor 1 HR1 antagonist widely used for allergic process that also acts through different intracellular signaling including AktMITF and PKCBII-tyrosine kinase Recent studies have demonstrated that co-treatment with loratadine sensitize KBV20C resistant cells to vincristine which improve the onco-therapeutical effect The primary study objective is to assess the safety profile of loratadine 10 mgday associated with the current standard treatment sirolimus and its potential benefit abrogating the lung function decline after 52 weeks of treatment The secondary objectives include a an assessment of quality of life and progression free-survival time and b to determine the clinical usefulness of the major histamine-derived metabolite methylimidazoleacetic acid MIAA for monitoring of disease progression and biological treatment effect
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None