LymphangioleiomyomatosisPhase 2LORALAMNCT05190627
Effect of Loratadine in Lymphangioleiomyomatosis
A Phase 2 study testing Loratadine in people with Lymphangioleiomyomatosis, run by Institut d'Investigació Biomèdica de Bellvitge at 6 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphangioleiomyomatosis
- What is being tested?
- Loratadine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 6 sitesSpain
- Study dates
- 1 Nov 2021to 30 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Written informed consent consistent with GCP and local laws signed prior to entry into the study.
- 2. Patients with LAM and > 18 years-old with:
- FEV1 > 35% and DLCO > 20%
- Oxygen saturation (SpO2) > 85% by pulse oximetry while breathing ambient air at rest
- Patients with a definite diagnosis consistent with LAM prior to screening based on International consensus criteria within 10 years prior to randomization
- HRCT within 12 months prior to randomization with central reading demonstrating a radiological pattern suggesting LAM and some other criteria for initiating sirolimus (symptoms, FEV1 decline or the presence of abdominal lynphangioleiomiomas).
Who cannot join
- Concomitant use of other HR1 antagonist
- Hypersensitivity to HR1 antagonists
- Current smoker or ex-smoker having quit smoking < 4 months prior to firs screening visit - Use of systemic immunosuppressants or chemotherapy within 30 days of screening.
- Receiving oral corticosteroids>15mg/day, vasodilator therapies for pulmonary hypertension (e.g., bosentan), unapproved and/or investigational therapies for LAM or administration of such therapies within 4 weeks of initial screening.
- At baseline/screening visit, values of liver transaminases above 3 times upper limit, alkaline phosphatase above 2.5 times upper limit, or bilirubin above 1.5 times upper limit
- Creatinine clearance (CrCl)<60ml/min (determined by Cockcroft-Gault Equation) at baseline/ screening visit.
Show all 9Show fewer
- Patients treated with strong inhibitors and inducers of CYP either during the study or 14 days prior to enrolment in the study: antifungals (e.g., ketoconazole, itraconazole), clarithromycin, telithromycin, cobicistat, protease inhibitors (e.g., atazanavir, ritonavir, and saquinavir) and grapefruit juice, phenytoin, carbamazepine, barbiturates, rifampin.
- Current allergic asthma or other major allergic diseases that requires different daily anti- histaminic treatment.
- History of coexistent and clinically significant (in the opinion of the Investigator) chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, inadequately treated sleep- disordered breathing, or any clinically significant pulmonary diseases other than LAM.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites, 4 recruiting
- Not yet recruiting
Hospital Vall d'Hebron
Barcelona
Bea Saez, MD
- Recruiting
University Hospital of Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Vanesa Vicens-Zygmunt, PI, 0034 932607689, ufip@bellvitgehospital.cat
- Active, not recruiting
Hospital La Princes
Madrid
- Active, not recruiting
Hospital Puerta de Hierro
Madrid
- Not yet recruiting
Hospital Marqués de Valdecillas
Santander
David Iturbe, MD, PhD
- Not yet recruiting
Hospital Virgen del Rocío
Seville
Jose Antonio Rodriguez Portal, MD, PhD
About this study
Official title: Phase II Clinical Trial Evaluating the Effect of Loratadine Associated to Rapamicyn in Patients With Lymphangioleiomyomatosis
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 1:1 to add oral loratadine 10mg/day 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)
Read the 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 (TSC1/2), 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 Akt/MITF 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 mg/day 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.
- Conditions
- Lymphangioleiomyomatosis
- Being tested
- Loratadine, Placebo 10mg/day added to rapamycin for 12 months
- Keywords
- LAM, Rapamycin, Loratadine
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LoratadineDrug
Also called Clarytine
Loratadine 10mg/day added to rapamycin for 12 months
Placebo 10mg/day added to rapamycin for 12 monthsDrug
Placebo in the same type of capsule than the experimental drug
| Study group | Role | What they receive |
|---|---|---|
| Loratadine treatment on rapamycin | Experimental | Loratadine (oral administration, daily dose 10mg) in LAM patients that are treated with rapamycin Receives: Drug: Loratadine |
| Placebo treatment on rapamycin | Placebo comparator | Placebo (oral administration, daily dose 10 mg) in LAM patients that are treated with rapamycin Receives: Drug: Placebo 10mg/day added to rapamycin for 12 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (safety) of loratadine in combination with sirolimus after 52 weeks of treatment
To compare the incidence of adverse events in LAM patients treated with sirolimus and loratadine versus sirolimus alone. Any adverse event related to both drugs, including nausea, diarrhea, stomach discomfort, vomiting, headache and liver hipertransaminasemia, will be evaluated.
Measured: 52 weeks
Secondary outcomes (6)
To evaluate the effect of loratadine associated with sirolimus on quality of life measured by the Saint George's Questionnaire
The Saint George's Questionnaire is one of the most validated questionnaires in respiratory diseases that evaluates three dimensions; symptoms, activity and disease impact, and the total score ranges from 0 (worse situation) to 100 (best situation).
Measured: 52 weeks
Study-drug discontinuation
To compare the rate of study-drug discontinuation during the study in both arms
Measured: 52 weeks
Serum levels of sirolimus
Analyzing the number of patients that maintain the serum levels of sirolimus on window range that is considered therapeutic and safe (5-15 pg).
Measured: 52 weeks
To evaluate the effect of loratadine associated with sirolimus on progression-free survival time
Progression-free survival time, which will be considered when some of these events are present: FEV1 decrease > 10%, DLCO decrease > 15%, lung transplant, death.
Measured: 52 weeks
To evaluate the effect of loratadine associated with sirolimus on hospitalization rate
Hospitalization. Registration of any cause of hospitalization.
Measured: 52 weeks
To evaluate the effect of loratadine associated with sirolimus on serum biomarkers
Serum biomarkers: measuring changes on the single established biomarker to date (VEGF-D)
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start1 Nov 2021
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphangioleiomyomatosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut d'Investigació Biomèdica de Bellvitge
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Molina, Institut d'Investigació Biomèdica de Bellvitge
- Investigators
- Maria Molina-Molina, MD, PhD, Study director, Institut d'Investigació Biomèdica de Bellvitge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05190627
- Sponsor's protocol ID
- LORALAM
- Acronym
- LORALAM
- Status last verified
- Jan 2022
- First submitted
- 11 Dec 2021
- Last updated
- 27 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial Evaluating the Effect of Loratadine Associated to Rapamicyn in Patients With Lymphangioleiomyomatosis
- ClinicalTrials.gov ID
- NCT05190627
- Acronym / sponsor ID
- LORALAM / LORALAM
- Conditions
- Lymphangioleiomyomatosis
- Keywords
- LAM, Rapamycin, Loratadine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Institut d'Investigació Biomèdica de BellvitgeUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 13 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 1:1 to add oral loratadine 10mg/day 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 (TSC1/2), 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 Akt/MITF 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 mg/day 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Loratadine treatment on rapamycin | Experimental | Drug: LoratadineLoratadine (oral administration, daily dose 10mg) in LAM patients that are treated with rapamycin |
| Placebo treatment on rapamycin | Placebo comparator | Drug: Placebo 10mg/day added to rapamycin for 12 monthsPlacebo (oral administration, daily dose 10 mg) in LAM patients that are treated with rapamycin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 1. Written informed consent consistent with GCP and local laws signed prior to entry into the study.
- FEV1 > 35% and DLCO > 20%
- Oxygen saturation (SpO2) > 85% by pulse oximetry while breathing ambient air at rest
- Patients with a definite diagnosis consistent with LAM prior to screening based on International consensus criteria within 10 years prior to randomization
- HRCT within 12 months prior to randomization with central reading demonstrating a radiological pattern suggesting LAM and some other criteria for initiating sirolimus (symptoms, FEV1 decline or the presence of abdominal lynphangioleiomiomas).
Key exclusion criteria (9 listed)
- Concomitant use of other HR1 antagonist
- Hypersensitivity to HR1 antagonists
- Current smoker or ex-smoker having quit smoking < 4 months prior to firs screening visit - Use of systemic immunosuppressants or chemotherapy within 30 days of screening.
- Receiving oral corticosteroids>15mg/day, vasodilator therapies for pulmonary hypertension (e.g., bosentan), unapproved and/or investigational therapies for LAM or administration of such therapies within 4 weeks of initial screening.
- At baseline/screening visit, values of liver transaminases above 3 times upper limit, alkaline phosphatase above 2.5 times upper limit, or bilirubin above 1.5 times upper limit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LoratadineAlso: ClarytineLoratadine 10mg/day added to rapamycin for 12 months | Drug | Loratadine treatment on rapamycin |
| Placebo 10mg/day added to rapamycin for 12 monthsPlacebo in the same type of capsule than the experimental drug | Drug | Placebo treatment on rapamycin |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (safety) of loratadine in combination with sirolimus after 52 weeks of treatment
Time frame: 52 weeks
To compare the incidence of adverse events in LAM patients treated with sirolimus and loratadine versus sirolimus alone. Any adverse event related to both drugs, including nausea, diarrhea, stomach discomfort, vomiting, headache and liver hipertransaminasemia, will be evaluated.
6 secondary outcomes
To evaluate the effect of loratadine associated with sirolimus on quality of life measured by the Saint George's Questionnaire
Time frame: 52 weeks
Study-drug discontinuation
Time frame: 52 weeks
Serum levels of sirolimus
Time frame: 52 weeks
To evaluate the effect of loratadine associated with sirolimus on progression-free survival time
Time frame: 52 weeks
To evaluate the effect of loratadine associated with sirolimus on hospitalization rate
Time frame: 52 weeks
To evaluate the effect of loratadine associated with sirolimus on serum biomarkers
Time frame: 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2022.
- IDIBELL webpageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Lymphangioleiomyomatosis
RecruitingPhase 1/2
Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis
Lymphangioleiomyomatosis
RecruitingObservational study
Study of the Disease Process of Lymphangioleiomyomatosis
Lung Disease, Pneumothorax
RecruitingObservational study
National Lymphangioleiomyomatosis Registry, France
Lymphangioleiomyomatosis
RecruitingObservational study
TSC Biosample Repository and Natural History Database
Tuberous Sclerosis, Lymphangioleiomyomatosis
RecruitingObservational study
Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)
Tuberous Sclerosis Complex, Lymphangioleiomyomatosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Molina-Molina, MD, PhD study director
Institut d'Investigació Biomèdica de Bellvitge
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Loratadine in people with Lymphangioleiomyomatosis, run by Institut d'Investigació Biomèdica de Bellvitge at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mar Chicote, PM (0034932607689, ufip@bellvitgehospital.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (safety) of loratadine in combination with sirolimus after 52 weeks of treatment (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2022.