Venous MalformationPhase 2EVANCT06788314
A Study of Enalapril in Treatment of Venous Malformations
A Phase 2 study testing Enalapril in people with Venous Malformation and Pain, run by Oslo University Hospital at 1 site in Norway.
Trial summary
The goal of this clinical trial is to explore if enalapril can be used to treat painful venous malformations. The main question it aims to answer are: Can enalapril reduce pain and volume of the malformation and increase quality of life in patients with painful venous malformations? Participants will: Receive a dose… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Venous Malformation, Pain, Quality of Life
- What is being tested?
- Enalapril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNorway
- Study dates
- 1 Feb 2025to 1 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with venous malformations verified by clinical examination, ultrasound and anatomic MRI with contrast. The venous malformation should have well defined borders and the volume should be measurable on MRI. Diagnosis of venous malformation shall be object for consensus in a multidisciplinary team meeting.
- Patients must experience pain from the malformation. Pain is defined as local pain in the malformation, and the participant must have pain that according to the patient inhibits daily activity or pain during nighttime that interferes with sleep. The symptoms has to reduces quality of life. NRS inclusion criteria is greater or equal to 4.
- Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
- Negative urine pregnancy test in females with childbearing potential. A woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
- Woman of childbearing potential (WOCBP) must use highly effective contraception measures while on study medicine and for up to 2 weeks past treatment:
- Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation.
- Progestogen-only hormonal contraception associated with inhibition of ovulation Intrauterine device (IUS) Intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomized partner Sexual abstinence (controlled with regular questioning by PI)
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF). They must also be capable of answer adequately questionnaires regarding quality of life. Since the questionnaire are validated in Norwegian and English they also should control one of this language.
Who cannot join
- Diffuse VM with no defined borders.
- Known diabetes because of the risk of hypoglycemia.
- Impaired liver function (INR > 1,5 or aminotransferases > 3 times upper limit of normal
- Use of mTOR-inhibitor, racekadotril, sacubitril/valsartan, ramipril or vildagliptin is contraindicated because of an elevated risk of angioedema
- Use of angiotensin-II receptor antagonist or alsikiren (direct renin inhibitor) is contraindicated because of increased risk of hypotension, hyperkalemia, and impaired renal function.
- Impaired cardiac function and clinically significant cardiac disease including aorta- and mitral valve stenosis and hypertrophic cardiomyopathy.
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- Lactose intolerance, total lactase deficiency or glucose-galactose malabsorption because Enalapril contains lactose.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the ACE-inhibitor (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea > grade 2, malabsorption syndrome, or small bowel resection.)
- Hypersensitivity to the active substance or any of the excipients listed in section 6.1 of the SmPC of enalpril or to other ACE-inhibitors.
- Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicated participation in the clinical study.
- Known renal artery stenosis.
- Patients with a history of angioneurotic edema related to previous treatment with ACE-inhibitors and patients with Hereditary or ideopatic anigioneurotic edema.
- Contraindications for MRI (cardiac pacemaker or defibrillator, intracranial clips, cochlear implants or other metallic foreign bodies, claustrophobia.
- BMI> 30
- Impaired kidney function (eGFR< 50)
- Pregnant or lactating woman
- Any condition that in the view of the investigator would suggest that the patient is unable to compley with the study protocol and procedures.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Norway1 site, 1 recruiting
- Recruiting
Oslo University Hospital, Rikshospitalet
Oslo, Norway
Christina Bjerring Opheim, MD, PhD candidate, 0047 23070000, chbjer@ous-hf.no
About this study
Official title: A Single Center, Single Arm, Phase 2, Pilot Study to Investigate the Efficacy of the ACE Inhibitor Enalapril in Participants Aged 18-70 Years of Age With Painful Venous Malformations.
The goal of this clinical trial is to explore if enalapril can be used to treat painful venous malformations. The main question it aims to answer are:
- Can enalapril reduce pain and volume of the malformation and increase quality of life in patients with painful venous malformations?
Read more
Participants will:
Receive a dose of enalapril 5 mg once daily. If it doesn't have effect the dose of enalapril will be increased to 10 mg daily after 3 months.
The treatment duration will be 12 months, with an additional follow-up of 12 months.
The visit frequency will be after 1, 3, 6,9 and 12 months and then a follow up visit at 18 and 24 months.
Approximately 15 participants will be screened to achieve minimum 10 enrolled participants.
Read the detailed description
Venous malformations are congenital defects of vasculature and may be disabling for patients throughout life, mostly because of disfigurement and pain. The patients remain challenging to treat as standard of care like sclerotherapy and compression garment is often inadequate in relieving the symptoms.
A chance observation has given reason to believe that enalapril may have the potential to reduce pain and volume in venous malformations. A young man with a symptomatic intramuscular venous malformation of the upper limp, and hypertension was treated with an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 8 months of treatment, it was registered a considerable volume reduction of the malformation and a reduction in pain.
Studies have reported that embryonic stem cell-like subpopulations in venous malformations express components of the renin-anigotensin system (RAS).
It has been hypothesized that such primitive cells could be a novel therapeutic target by manipulation of the RAS using ACE-inhibitors.
The aim of the study is to explore if the chance observation of reduced pain and volume of a venous malformation after enalapril treatment is a coincidence, or if enalapril may play a future role in the treatment of venous malformations.
- Conditions
- Venous Malformation, Pain, Quality of Life, Vascular Malformation
- Being tested
- Enalapril
- Medical subject headings
- Pain, Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnalaprilDrug
Each participant will receive a dose of enalapril 5 mg once daily. If the participant doesn't have effect of the intervention after 3 months, the dose of enalapril will be increased to 10 mg daily, if the tolerance of enalapril is good. Lack of effect will be defined as unchanged or increased NRS score.
Treatment duration will be 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Enalapril | Experimental | Not described Receives: Drug: Enalapril |
What is being measured
The primary outcome is the main question the study is designed to answer.
To explore the change of venous malformation related pain
Changes in NRS (Numeric rating scale). NRS is an analogue scale with numbers from 0-10, where 0 represents no pain and 10 represents the worst imaginable pain.
Measured: From baseline and to the end of treatment at 12 months.
Secondary outcomes (3)
To explore volume change of the venous malformation
Volume will be assessed by MRI. To estimate the volume of the venous malformation the area of the malformation on multiple adjacent MRI slices will be added and multiplied by the slice thickness. The volume change at follow-up imaging is calculated according to this formula: (Volume at baseline - volume at follow up)/ (volume at baseline) x 100 = percentage volume change.
Measured: From baseline to the end of treatment at 12 months.
To explore change in quality of life in patients with venous malformations
Quality of life, will be assessed by the SF-36 (Short Form) questionnaire. The SF-36 consists of 36 questions measuring quality of life in 4 mental domains and 4 physical domains, supplying general information about life quality. The score of the SF-36 ranging from 0-100. Higher score ranging better health status.
Measured: From baseline to the end of treatment at 12 months.
To explore change in quality of life in patients with venous malformations
Quality of life, will be assessed by the OVAMA score (Outcome measures for vascular malformations).
The OVAMA score is a disease specific patient-reported-outcome-measures consisting of 23 questions measuring quality of live with a general symptom scale with 6 items, a head and neck symptom scale with 8 items, and an appearance scale with 9 items.
Measured: From baseline to the end of treatment at 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2025
- Study start1 Feb 2025
- Primary completion1 Dec 2029 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Venous MalformationStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective pilot study
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christina Elisabeth Bjerring Opheim, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06788314
- Sponsor's protocol ID
- 2023-510076-31-00
- Other IDs
- 2023
- Acronym
- EVA
- Status last verified
- Feb 2025
- First submitted
- 10 Jan 2025
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data protection officer in Norway does not allow it.
Publications
Siljee S, Keane E, Marsh R, Brasch HD, Tan ST, Itinteang T. Expression of the Components of the Renin-Angiotensin System in Venous Malformation. Front Surg. 2016 May 3;3:24. doi: 10.3389/fsurg.2016.00024. eCollection 2016.
PubMed 27200356Tan EMS, Siljee SD, Brasch HD, Enriquez S, Tan ST, Itinteang T. Embryonic Stem Cell-Like Subpopulations in Venous Malformation. Front Med (Lausanne). 2017 Oct 4;4:162. doi: 10.3389/fmed.2017.00162. eCollection 2017.
PubMed 29046873Tan EMS, Brasch HD, Davis PF, Itinteang T, Tan ST. Embryonic Stem Cell-like Population within Venous Malformation Expresses the Renin-Angiotensin System. Plast Reconstr Surg Glob Open. 2019 Apr 2;7(4):e2170. doi: 10.1097/GOX.0000000000002170. eCollection 2019 Apr.
PubMed 31321175Berger S, Bjark TH, Midtvedt K, Andersen R. Regression of a venous malformation during angiotensin-converting enzyme inhibitor treatment for hypertension. J Vasc Surg Cases Innov Tech. 2022 Sep 17;8(4):657-659. doi: 10.1016/j.jvscit.2022.09.004. eCollection 2022 Dec.
PubMed 36262918
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Single Arm, Phase 2, Pilot Study to Investigate the Efficacy of the ACE Inhibitor Enalapril in Participants Aged 18-70 Years of Age With Painful Venous Malformations.
- ClinicalTrials.gov ID
- NCT06788314
- Acronym / sponsor ID
- EVA / 2023-510076-31-00
- Conditions
- Venous Malformation, Pain, Quality of Life, Vascular Malformation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 1 Feb 2025 (actual)
- Primary completion
- 1 Dec 2029 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 23 Jan 2025 (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.
The goal of this clinical trial is to explore if enalapril can be used to treat painful venous malformations. The main question it aims to answer are:
- Can enalapril reduce pain and volume of the malformation and increase quality of life in patients with painful venous malformations?
Participants will:
Receive a dose of enalapril 5 mg once daily. If it doesn't have effect the dose of enalapril will be increased to 10 mg daily after 3 months.
The treatment duration will be 12 months, with an additional follow-up of 12 months.
The visit frequency will be after 1, 3, 6,9 and 12 months and then a follow up visit at 18 and 24 months.
Approximately 15 participants will be screened to achieve minimum 10 enrolled participants.
Detailed description
Venous malformations are congenital defects of vasculature and may be disabling for patients throughout life, mostly because of disfigurement and pain. The patients remain challenging to treat as standard of care like sclerotherapy and compression garment is often inadequate in relieving the symptoms.
A chance observation has given reason to believe that enalapril may have the potential to reduce pain and volume in venous malformations. A young man with a symptomatic intramuscular venous malformation of the upper limp, and hypertension was treated with an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 8 months of treatment, it was registered a considerable volume reduction of the malformation and a reduction in pain.
Studies have reported that embryonic stem cell-like subpopulations in venous malformations express components of the renin-anigotensin system (RAS).
It has been hypothesized that such primitive cells could be a novel therapeutic target by manipulation of the RAS using ACE-inhibitors.
The aim of the study is to explore if the chance observation of reduced pain and volume of a venous malformation after enalapril treatment is a coincidence, or if enalapril may play a future role in the treatment of venous malformations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective pilot study
| Arm | Type | Receives |
|---|---|---|
| Enalapril | Experimental | Drug: Enalapril |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with venous malformations verified by clinical examination, ultrasound and anatomic MRI with contrast. The venous malformation should have well defined borders and the volume should be measurable on MRI. Diagnosis of venous malformation shall be object for consensus in a multidisciplinary team meeting.
- Patients must experience pain from the malformation. Pain is defined as local pain in the malformation, and the participant must have pain that according to the patient inhibits daily activity or pain during nighttime that interferes with sleep. The symptoms has to reduces quality of life. NRS inclusion criteria is greater or equal to 4.
- Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
- Negative urine pregnancy test in females with childbearing potential. A woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
- Woman of childbearing potential (WOCBP) must use highly effective contraception measures while on study medicine and for up to 2 weeks past treatment:
Key exclusion criteria (17 listed)
- Diffuse VM with no defined borders.
- Known diabetes because of the risk of hypoglycemia.
- Impaired liver function (INR > 1,5 or aminotransferases > 3 times upper limit of normal
- Use of mTOR-inhibitor, racekadotril, sacubitril/valsartan, ramipril or vildagliptin is contraindicated because of an elevated risk of angioedema
- Use of angiotensin-II receptor antagonist or alsikiren (direct renin inhibitor) is contraindicated because of increased risk of hypotension, hyperkalemia, and impaired renal function.
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 |
|---|---|---|
| EnalaprilEach participant will receive a dose of enalapril 5 mg once daily. If the participant doesn't have effect of the intervention after 3 months, the dose of enalapril will be increased to 10 mg daily, if the tolerance of enalapril is good. Lack of effect will be defined as unchanged or increased NRS score. Treatment duration will be 12 months. | Drug | Enalapril |
Primary outcome
To explore the change of venous malformation related pain
Time frame: From baseline and to the end of treatment at 12 months.
Changes in NRS (Numeric rating scale). NRS is an analogue scale with numbers from 0-10, where 0 represents no pain and 10 represents the worst imaginable pain.
3 secondary outcomes
To explore volume change of the venous malformation
Time frame: From baseline to the end of treatment at 12 months.
To explore change in quality of life in patients with venous malformations
Time frame: From baseline to the end of treatment at 12 months.
To explore change in quality of life in patients with venous malformations
Time frame: From baseline to the end of treatment at 12 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Background: PubMed 27200356Siljee S, Keane E, Marsh R, Brasch HD, Tan ST, Itinteang T. Expression of the Components of the Renin-Angiotensin System in Venous Malformation. Front Surg. 2016 May 3;3:24. doi: 10.3389/fsurg.2016.00024. eCollection 2016.
- Background: PubMed 29046873Tan EMS, Siljee SD, Brasch HD, Enriquez S, Tan ST, Itinteang T. Embryonic Stem Cell-Like Subpopulations in Venous Malformation. Front Med (Lausanne). 2017 Oct 4;4:162. doi: 10.3389/fmed.2017.00162. eCollection 2017.
- Background: PubMed 31321175Tan EMS, Brasch HD, Davis PF, Itinteang T, Tan ST. Embryonic Stem Cell-like Population within Venous Malformation Expresses the Renin-Angiotensin System. Plast Reconstr Surg Glob Open. 2019 Apr 2;7(4):e2170. doi: 10.1097/GOX.0000000000002170. eCollection 2019 Apr.
- Background: PubMed 36262918Berger S, Bjark TH, Midtvedt K, Andersen R. Regression of a venous malformation during angiotensin-converting enzyme inhibitor treatment for hypertension. J Vasc Surg Cases Innov Tech. 2022 Sep 17;8(4):657-659. doi: 10.1016/j.jvscit.2022.09.004. eCollection 2022 Dec.
- Individual participant dataSharing planned: No. The data protection officer in Norway does not allow it.
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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.
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 Enalapril in people with Venous Malformation and Pain, run by Oslo University Hospital at 1 site in Norway.
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 8 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 2 Apr 2025. 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 Norway. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christina Bjerring Opheim, MD and PhD student (+47 23070000, chbjer@ous-hf.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To explore the change of venous malformation related pain (time frame: From baseline and to the end of treatment at 12 months.). 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 NCT06788314, which also lists 4 linked publications.
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 2 Apr 2025.