Lingual Microcystic Lymphatic MalformationsPhase 2TOPGUNNCT04128722
TOPical Sirolimus in linGUal Microcystic Lymphatic Malformation -TOPGUN
A Phase 2 study testing Sirolimus Oral Liquid Product 1mg/mL in people with Lingual Microcystic Lymphatic Malformations, run by University Hospital, Tours at 2 sites in France.
Trial summary
Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations, presenting as clusters of cysts filled with lymph fluid or blood. They are responsible for a heavy burden even with small well-limited lesions because of oozing, bleeding, infections, or even speech, chewing or breathing… Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Lingual Microcystic Lymphatic Malformations
- What is being tested?
- Sirolimus Oral Liquid Product 1mg/mL
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesFrance
- Study dates
- 14 Feb 2020to 8 Jan 2025
- 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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants ≥ 5 years of age
- Lingual microcystic lymphatic malformation that does not require systemic treatment, assessed by clinical examination and head-and-neck MRI imaging prior to study enrolment, with or without underlying syndromic malformation (CLAPO for instance)
- Participants covered by or having the rights to social security
- Written informed consent obtained from participant and participant's legal representative if participant is under 18
- Ability for participant to comply with the requirements of the study
Who cannot join
- Patients with a lymphatic malformation requiring a continued background therapy (involving deep organs)
- Secondary lymphatic malformations (lymphangiectasia post-radiotherapy, etc)
- Previous treatment with systemic or topical mTOR (mammilian target of rapamycin) inhibitors within 12 months before inclusion (half-life of oral sirolimus is 60 days in adults).
- Previous treatment with oral or topical steroids within 10 days before inclusion (half-life of corticosteroids is 12-36 hours)
- Immunosuppression (immunosuppressive disease or immunosuppressive treatment)
- Ongoing neoplasia
Show all 14Show fewer
- Active chronic infectious disease (Hepatitis-B virus, Hepatitis-C virus, HIV, etc)
- Local necrosis
- Local fungal, viral (herpes simplex virus, varicella zoster virus, etc) or bacterial infection on the site of the LMLM (based on clinical examination)
- Known allergy to one of the components of the sirolimus solution
- Soy bean or Peanut allergy
- Pregnant or breastfeeding women
- Women of child-bearing potential (including teenagers) not using a reliable contraceptive method until the end of the study and three month after the end of the study or sirolimus discontinuation.
- Already involved in another therapeutic trial
Trial locations and contacts
2 sites in 1 country.
France2 sites
Hospital NECKER -AP-HP - Dermatology
Paris, 75015
Univsersity of TOURS _ Service de Dermatologie
Tours, Indre et Loire, 37044
About this study
Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations, presenting as clusters of cysts filled with lymph fluid or blood. They are responsible for a heavy burden even with small well-limited lesions because of oozing, bleeding, infections, or even speech, chewing or breathing impairment. Pain and aesthetic prejudice are also frequently reported. The natural history of LMLMs is progressive worsening. LMLMs complex management requires multidisciplinary care in specialised centres, and the "wait-and-see" approach is frequently used. In complicated lymphatic malformations, whatever the location, treatment with oral sirolimus, an mTOR (mammalian Target of Rapamycin) inhibitor, is often used.
Topical sirolimus is a known effective treatment for some cutaneous conditions such as angiofibromas in tuberous sclerosis. Topical applications of sirolimus on the buccal mucosae have been reported in erosive lichen planus and oral pemphigus vulgaris with good tolerance and none to slight detectable blood sirolimus concentrations.
The objective of this study is to evaluate the efficacy and safety of a 1mg/mL sirolimus solution applied once daily on mild to moderate lingual microcystic lymphatic malformation in children and adults after 4, 8, 12, 16, 20 and 24 weeks of treatment as compared to usual care (no treatment).
Read the detailed description
This is a randomized, open-labelled, multicenter pilot study using an individually randomized stepped wedge design over a 24 weeks period to evaluate topical application of 1 mg/mL sirolimus solution, 0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation that do not require systemic treatment, the experimental intervention versus usual care (no treatment), the control condition.
In this design, subjects are included in a cohort where at a randomized time (W0, W4, W8 or W12), they switch from an observational period to the interventional period.
All subjects will be followed for 24 weeks
- Being tested
- Sirolimus Oral Liquid Product 1mg/mL
- Keywords
- LMLM, Sirolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus Oral Liquid Product 1mg/mLDrug
Also called Experimental treatment
0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus 1mg/mL | Experimental | Application of 1 mg/mL sirolimus solution, 0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation, the experimental intervention versus usual care (no treatment), the control condition. Receives: Drug: Sirolimus Oral Liquid Product 1mg/mL |
| Control condition | No intervention | Usual care, i.e. no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Physical Global Assessment (PGA) after topical application of Sirolimus for 12 weeks
The primary outcome will consist in the evaluation of global severity of the LMLM using PGA (Physical Global Assessment) 0 to 5 score, by three independent blinded experts, on monthly standardized photographs.
A 1-point improvement versus baseline in PGA scale would already have a clinical relevance.
Our primary analysis will focus on change in PGA after topical application of Sirolimus for 12 weeks
Measured: 12 weeks
Secondary outcomes (10)
Investigator-assessed PGA
Investigator-assessed PGA (Physical Global Assessment)
Measured: at weeks 0, 4, 8, 12, 16, 20 and 24
Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort,
Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort, each using a numeric scale from 0 to 10 (0: clear, 10: very severe), at weeks 0, 4, 8, 12, 16, 20 and 24
Measured: at weeks 0, 4, 8, 12, 16, 20 and 24.
Global evolution assessed by the patient
Global evolution assessed by the patient from -10 to 10 (-10 = severe worsening, 0 = no change, 10 = complete recovery), at weeks 4, 8, 12, 16, 20 and 24.
Measured: at weeks 4, 8, 12, 16, 20 and 24.
Global Quality of life assessment
(DLQI or children's DLQI for minors aged 5 to 16), at baseline, time of switch to treatment and week 24.
Measured: at baseline, at time of switch to the intervention (either week 0, week 4, week 8 or week 12) and week 24.
Measurements of the lesion
by the investigator, at baseline, time of switch to treatment and week 24.
Measured: at baseline, at time of switch to the intervention (either week 0, week 4, week 8 or week 12) and week 24.
Time to obtain optimal results
i.e. time from switch to treatment to time reaching the minimal PGA score
Measured: up to 24 weeks
Assessment of tolerance of topical sirolimus:
record of local side effects at each visit after the patient has crossed over to the intervention, up to 24 weeks
Measured: from the switch to intervention up to the end of the study, i.e a maximum of 24 weeks.
General side effects
Follow-up of general side effects
Measured: rom the switch to intervention up to the end of the study, i.e a maximum of 24 weeks.
Assessment of sirolimus blood passage
by measuring residual sirolimus blood concentration: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until week 24
Measured: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until week 24
Evaluation of biological safety
Number of participants with at least one biological abnormality treatment-related adverse events as assessed by CTCAE v4.0
Measured: after 8,16 and up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2019
- Study start14 Feb 2020
- Primary completion8 Jan 2025
- Study completion8 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lingual Microcystic Lymphatic MalformationsStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- 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
- Crossover
- Model description
- Individually randomized stepped wedge
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Annabel MARUANI, MD-PhD, Study director, University Hospital of TOURS;INSERM 1246 SPHERE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04128722
- Sponsor's protocol ID
- DR190041-TOPGUN
- Other IDs
- 2019-001530-33, 2019
- Acronym
- TOPGUN
- Status last verified
- Nov 2025
- First submitted
- 24 Sep 2019
- Last updated
- 24 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marchand A, Caille A, Gissot V, Giraudeau B, Lengelle C, Bourgoin H, Largeau B, Leducq S, Maruani A. Topical sirolimus solution for lingual microcystic lymphatic malformations in children and adults (TOPGUN): study protocol for a multicenter, randomized, assessor-blinded, controlled, stepped-wedge clinical trial. Trials. 2022 Jul 8;23(1):557. doi: 10.1186/s13063-022-06365-y.
PubMed 35804404
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TOPical Sirolimus in linGUal Microcystic Lymphatic Malformation -TOPGUN
- ClinicalTrials.gov ID
- NCT04128722
- Acronym / sponsor ID
- TOPGUN / DR190041-TOPGUN
- Keywords
- LMLM, Sirolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 14 Feb 2020 (actual)
- Primary completion
- 8 Jan 2025 (actual)
- Study completion
- 8 Jan 2025 (actual)
- First posted
- 16 Oct 2019 (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.
Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations, presenting as clusters of cysts filled with lymph fluid or blood. They are responsible for a heavy burden even with small well-limited lesions because of oozing, bleeding, infections, or even speech, chewing or breathing impairment. Pain and aesthetic prejudice are also frequently reported. The natural history of LMLMs is progressive worsening. LMLMs complex management requires multidisciplinary care in specialised centres, and the "wait-and-see" approach is frequently used. In complicated lymphatic malformations, whatever the location, treatment with oral sirolimus, an mTOR (mammalian Target of Rapamycin) inhibitor, is often used.
Topical sirolimus is a known effective treatment for some cutaneous conditions such as angiofibromas in tuberous sclerosis. Topical applications of sirolimus on the buccal mucosae have been reported in erosive lichen planus and oral pemphigus vulgaris with good tolerance and none to slight detectable blood sirolimus concentrations.
The objective of this study is to evaluate the efficacy and safety of a 1mg/mL sirolimus solution applied once daily on mild to moderate lingual microcystic lymphatic malformation in children and adults after 4, 8, 12, 16, 20 and 24 weeks of treatment as compared to usual care (no treatment).
Detailed description
This is a randomized, open-labelled, multicenter pilot study using an individually randomized stepped wedge design over a 24 weeks period to evaluate topical application of 1 mg/mL sirolimus solution, 0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation that do not require systemic treatment, the experimental intervention versus usual care (no treatment), the control condition.
In this design, subjects are included in a cohort where at a randomized time (W0, W4, W8 or W12), they switch from an observational period to the interventional period.
All subjects will be followed for 24 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Individually randomized stepped wedge
| Arm | Type | Receives |
|---|---|---|
| Sirolimus 1mg/mL | Experimental | Drug: Sirolimus Oral Liquid Product 1mg/mLApplication of 1 mg/mL sirolimus solution, 0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation, the experimental intervention versus usual care (no treatment), the control condition. |
| Control condition | No intervention | –Usual care, i.e. no intervention |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Participants ≥ 5 years of age
- Lingual microcystic lymphatic malformation that does not require systemic treatment, assessed by clinical examination and head-and-neck MRI imaging prior to study enrolment, with or without underlying syndromic malformation (CLAPO for instance)
- Participants covered by or having the rights to social security
- Written informed consent obtained from participant and participant's legal representative if participant is under 18
- Ability for participant to comply with the requirements of the study
Key exclusion criteria (14 listed)
- Patients with a lymphatic malformation requiring a continued background therapy (involving deep organs)
- Secondary lymphatic malformations (lymphangiectasia post-radiotherapy, etc)
- Previous treatment with systemic or topical mTOR (mammilian target of rapamycin) inhibitors within 12 months before inclusion (half-life of oral sirolimus is 60 days in adults).
- Previous treatment with oral or topical steroids within 10 days before inclusion (half-life of corticosteroids is 12-36 hours)
- Immunosuppression (immunosuppressive disease or immunosuppressive treatment)
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 |
|---|---|---|
| Sirolimus Oral Liquid Product 1mg/mLAlso: Experimental treatment0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation | Drug | Sirolimus 1mg/mL |
Primary outcome
Change in Physical Global Assessment (PGA) after topical application of Sirolimus for 12 weeks
Time frame: 12 weeks
The primary outcome will consist in the evaluation of global severity of the LMLM using PGA (Physical Global Assessment) 0 to 5 score, by three independent blinded experts, on monthly standardized photographs. A 1-point improvement versus baseline in PGA scale would already have a clinical relevance. Our primary analysis will focus on change in PGA after topical application of Sirolimus for 12 weeks
10 secondary outcomes
Investigator-assessed PGA
Time frame: at weeks 0, 4, 8, 12, 16, 20 and 24
Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort,
Time frame: at weeks 0, 4, 8, 12, 16, 20 and 24.
Global evolution assessed by the patient
Time frame: at weeks 4, 8, 12, 16, 20 and 24.
Global Quality of life assessment
Time frame: at baseline, at time of switch to the intervention (either week 0, week 4, week 8 or week 12) and week 24.
Measurements of the lesion
Time frame: at baseline, at time of switch to the intervention (either week 0, week 4, week 8 or week 12) and week 24.
Time to obtain optimal results
Time frame: up to 24 weeks
Assessment of tolerance of topical sirolimus:
Time frame: from the switch to intervention up to the end of the study, i.e a maximum of 24 weeks.
General side effects
Time frame: rom the switch to intervention up to the end of the study, i.e a maximum of 24 weeks.
Assessment of sirolimus blood passage
Time frame: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until week 24
Evaluation of biological safety
Time frame: after 8,16 and up to 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2025.
- Derived from this study: PubMed 35804404Marchand A, Caille A, Gissot V, Giraudeau B, Lengelle C, Bourgoin H, Largeau B, Leducq S, Maruani A. Topical sirolimus solution for lingual microcystic lymphatic malformations in children and adults (TOPGUN): study protocol for a multicenter, randomized, assessor-blinded, controlled, stepped-wedge clinical trial. Trials. 2022 Jul 8;23(1):557. doi: 10.1186/s13063-022-06365-y.
- Individual participant dataSharing planned: No
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.
Annabel MARUANI, MD-PhD study director
University Hospital of TOURS;INSERM 1246 SPHERE
2 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 Sirolimus Oral Liquid Product 1mg/mL in people with Lingual Microcystic Lymphatic Malformations, run by University Hospital, Tours at 2 sites in France.
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 5 inclusion and 14 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: finished, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Physical Global Assessment (PGA) after topical application of Sirolimus for 12 weeks (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04128722, which also lists 1 linked publication.
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 24 Nov 2025.