Neurofibromatosis 1Phase 2NCT03090971
Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With NF1
A Phase 2 study testing Diclofenac Sodium and Saline Solution in people with Neurofibromatosis 1 and Cutaneous Neurofibroma, run by Fundação Educacional Serra dos Órgãos at 1 site in Brazil.
Trial summary
This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis 1, Cutaneous Neurofibroma
- What is being tested?
- Diclofenac Sodium and Saline Solution
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteBrazil
- Study dates
- 15 Feb 2017to 30 Jun 2017
- 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
- Adults of both genders, between the ages of 18 and 65;
- NF1, diagnosed clinically by a neurologist, dermatologist, or other specialist knowledgeable about the disease, and defined as:
- A known mutation in the gene coding for neurofibromin
- or, the presence of 2 of the following 7 clinical manifestations of NF1:
- ≥ 6 café-au-lait macules on the body with diameters greater than 15mm in the greatest diameter;
- two or more neurofibromas of any type or one plexiform neurofibroma
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- inguinal or axillary freckling
- two or more Lisch nodules (iris hamartomas)
- optic glioma
- a distinct osseous lesion, such as sphenoid wing dysplasia, pseudoarthrosis of the tibia, macrocephaly, or scoliosis
- a first-degree relative with NF1
- Presence of 4 or more cutaneous neurofibromas measuring 0.5-1.2cm in greatest diameter, present on thorax/abdomen or upper or lower limbs;
- If a woman of childbearing potential, is willing to use a medically acceptable form of contraception (in the judgment of the investigator) for the duration of the study;
- Is able to understand the informed consent form describing the risks of this study, and voluntarily signs the informed consent document;
- Is able to understand and comply with the requirements of the protocol.
Who cannot join
- Surgical, medical, or investigative treatment for any of the 6 target cutaneous neurofibromas to be evaluated in the study within three months prior to the baseline visit;
- Active infection (bacterial, viral, or fungal) requiring systemic antibiotics within two weeks of the baseline visit;
- Pregnancy or breastfeeding;
- Immunocompromised because of a medical condition;
- Known hypersensitivity to diclofenac or any other NSAID;
- Known hypersensitivity to aspirin;
Show all 18Show fewer
- has a known hypersensitivity to mannitol, sodium metabisulphite, benzyl alcohol, or propylene glycol;
- Known hypersensitivity to lidocaine;
- Currently receiving or has received with 2 weeks of screening an NSAID (including diclofenac), a COX-2 inhibitor, cyclosporine, methotrexate, an oral anti-diabetic, lithium, digoxin, diuretics, anticoagulants (such as warfarin), or a quinolone antibiotic; except for intralesional diclofenac, these medications will not be allowed during the study; low-dose aspirin used for cardioprotective effects will be allowed;
- Any history of hepatic (including hepatic porphyria) or renal disease resulting in ongoing compromised hepatic or renal function;
- History of a bleeding/coagulation disorder;
- History of gastrointestinal (gastric or intestinal) ulcer disease, Crohn's disease, or ulcerative colitis;
- Laboratory examination at screening that reveals in the opinion of the investigator significant, unstable, and/or untreated renal, hepatic, or metabolic disease/dysfunction;
- White blood cell count at screening that is less than 3000, or a platelet count at screening that is less than 150,000;
- Laboratory evaluation at screening that shows the hemoglobin lower than the lower limit of normal for the laboratory utilized;
- Under treatment for a medical condition that, in the opinion of the investigator, may interfere with the safety of the experimental treatment or with the evaluation of efficacy, including but not limited to cardiovascular and/or respiratory disease;
- Subject is not, in the opinion of the investigator, capable of giving informed consent to participate in the study;
- Subject has received an investigational therapy or procedure for any reason within 30 days prior to screening.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Fundação Educacional Serra dos Órgãos - UNIFESO
Teresópolis, Rio de Janeiro, 25964-000
About this study
Official title: Clinical Assessment of the Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With Neurofibromatosis Type 1
This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 \& 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 at 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period.
Read the detailed description
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome with highly variable clinical manifestations and that has a worldwide incidence of approximately 1/2500. The most common lesion is the cutaneous neurofibroma, appearing on the skin of 90% of adults with NF1. The number of cutaneous neurofibromas in an affected individual can vary from a few to several thousand. These lesions may be surgically removed, but typically recur, and surgical removal often leads to scarring. Intralesional administration of diclofenac was previously reported with favorable results, and significant inflammatory processes were observed within the treated neurofibromas, with tissue necrosis and detachment of some treated neurofibromas, effects that were not observed among the control neurofibromas. The primary objective of this study is to evaluate the use of topical diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. The secondary objective of this study is to assess the safety of the use of topical diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 \& 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period. Prior to any study-related procedure, written informed consent will be obtained from the participant. The Clinical Research From will be filled, stored, coded, and the data will be analyzed using GraphPad Prism, v. 5.0. Frequency tables will be generated and central tendencies calculated (mean, median, mode).
- Conditions
- Neurofibromatosis 1, Cutaneous Neurofibroma
- Being tested
- Diclofenac Sodium, Saline Solution
- Medical subject headings
- Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diclofenac SodiumDrug
Following microporation, treatment neurofibromas will receive treatment with topical diclofenac
Saline SolutionDrug
Following microporation, control neurofibromas will receive treatment with topical saline
| Study group | Role | What they receive |
|---|---|---|
| Cutaneous neurofibromas | Experimental | Each subject will have two treatment neurofibromas and two control neurofibromas. Following microporation, the two treatment neurofibromas will be treated with topical diclofenac while the two control neurofibromas will be treated with topical saline. Receives: Drug: Diclofenac Sodium; Drug: Saline Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy - presence of inflammatory process in the treated neurofibromas
Inflammatory process (redness, exculceration)
Measured: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Secondary outcomes (4)
Efficacy - presence of tissue necrosis in treated neurofibromas
Presence of tissue necrosis in treated neurofibromas
Measured: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Efficacy - neurofibroma size
Reduction in neurofibroma size
Measured: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Efficacy - neurofibroma detatchment
Detachment of the treated neurofibroma
Measured: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Safety - Adverse events
Occurrence of adverse events considered to be associated with the study drug
Measured: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start15 Feb 2017
- Primary completion23 Mar 2017
- Study completion30 Jun 2017
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 Neurofibromatosis 1Studies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundação Educacional Serra dos Órgãos
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mauro Geller, Fundação Educacional Serra dos Órgãos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090971
- Sponsor's protocol ID
- NX101-02-2016
- Status last verified
- Oct 2017
- First submitted
- 8 Mar 2017
- Last updated
- 26 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Oliveira LB, Geller M, Cunha KS, Santos A, Bernacchi A, Rubenstein AE, Takirambudde S, Mezitis S, de Almeida Ito Brum C, Darrigo LG Jr, Ribeiro MG. Clinical assessment of the use of topical liquid diclofenac following laser microporation of cutaneous neurofibromas in individuals with neurofibromatosis type 1. Heliyon. 2021 Mar 17;7(3):e06518. doi: 10.1016/j.heliyon.2021.e06518. eCollection 2021 Mar.
PubMed 33817379
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Assessment of the Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With Neurofibromatosis Type 1
- ClinicalTrials.gov ID
- NCT03090971
- Acronym / sponsor ID
- NX101-02-2016
- Conditions
- Neurofibromatosis 1, Cutaneous Neurofibroma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Fundação Educacional Serra dos ÓrgãosUniversity, hospital or other
- Study start
- 15 Feb 2017 (actual)
- Primary completion
- 23 Mar 2017 (actual)
- Study completion
- 30 Jun 2017 (actual)
- First posted
- 27 Mar 2017 (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.
This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 \& 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 at 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period.
Detailed description
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome with highly variable clinical manifestations and that has a worldwide incidence of approximately 1/2500. The most common lesion is the cutaneous neurofibroma, appearing on the skin of 90% of adults with NF1. The number of cutaneous neurofibromas in an affected individual can vary from a few to several thousand. These lesions may be surgically removed, but typically recur, and surgical removal often leads to scarring. Intralesional administration of diclofenac was previously reported with favorable results, and significant inflammatory processes were observed within the treated neurofibromas, with tissue necrosis and detachment of some treated neurofibromas, effects that were not observed among the control neurofibromas. The primary objective of this study is to evaluate the use of topical diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. The secondary objective of this study is to assess the safety of the use of topical diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 \& 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period. Prior to any study-related procedure, written informed consent will be obtained from the participant. The Clinical Research From will be filled, stored, coded, and the data will be analyzed using GraphPad Prism, v. 5.0. Frequency tables will be generated and central tendencies calculated (mean, median, mode).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cutaneous neurofibromas | Experimental | Drug: Diclofenac Sodium, Drug: Saline SolutionEach subject will have two treatment neurofibromas and two control neurofibromas. Following microporation, the two treatment neurofibromas will be treated with topical diclofenac while the two control neurofibromas will be treated with topical saline. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Adults of both genders, between the ages of 18 and 65;
- NF1, diagnosed clinically by a neurologist, dermatologist, or other specialist knowledgeable about the disease, and defined as:
- A known mutation in the gene coding for neurofibromin
- ≥ 6 café-au-lait macules on the body with diameters greater than 15mm in the greatest diameter;
- two or more neurofibromas of any type or one plexiform neurofibroma
Key exclusion criteria (18 listed)
- Surgical, medical, or investigative treatment for any of the 6 target cutaneous neurofibromas to be evaluated in the study within three months prior to the baseline visit;
- Active infection (bacterial, viral, or fungal) requiring systemic antibiotics within two weeks of the baseline visit;
- Pregnancy or breastfeeding;
- Immunocompromised because of a medical condition;
- Known hypersensitivity to diclofenac or any other NSAID;
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 |
|---|---|---|
| Diclofenac SodiumFollowing microporation, treatment neurofibromas will receive treatment with topical diclofenac | Drug | Cutaneous neurofibromas |
| Saline SolutionFollowing microporation, control neurofibromas will receive treatment with topical saline | Drug | Cutaneous neurofibromas |
Primary outcome
Efficacy - presence of inflammatory process in the treated neurofibromas
Time frame: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Inflammatory process (redness, exculceration)
4 secondary outcomes
Efficacy - presence of tissue necrosis in treated neurofibromas
Time frame: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Efficacy - neurofibroma size
Time frame: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Efficacy - neurofibroma detatchment
Time frame: Throughout the 7-day treatment period and subsequent 30-day follow-up period
Safety - Adverse events
Time frame: Throughout the 7-day treatment period and subsequent 30-day follow-up period
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 26 Oct 2017.
- Derived from this study: PubMed 33817379Oliveira LB, Geller M, Cunha KS, Santos A, Bernacchi A, Rubenstein AE, Takirambudde S, Mezitis S, de Almeida Ito Brum C, Darrigo LG Jr, Ribeiro MG. Clinical assessment of the use of topical liquid diclofenac following laser microporation of cutaneous neurofibromas in individuals with neurofibromatosis type 1. Heliyon. 2021 Mar 17;7(3):e06518. doi: 10.1016/j.heliyon.2021.e06518. eCollection 2021 Mar.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diclofenac Sodium and Saline Solution in people with Neurofibromatosis 1 and Cutaneous Neurofibroma, run by Fundação Educacional Serra dos Órgãos at 1 site in Brazil.
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 15 inclusion and 18 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 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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?
Efficacy - presence of inflammatory process in the treated neurofibromas (time frame: Throughout the 7-day treatment period and subsequent 30-day follow-up period). 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 NCT03090971, 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 26 Oct 2017.