Using enalapril to treat painful venous malformations

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.

This study is testing if the medication enalapril can help reduce pain and size of painful venous malformations in patients over a year.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Oslo University Hospital (other)
• Locations: 1 site (Oslo, Norway)
• Trial ID: NCT06788314 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of enalapril, an ACE inhibitor, in treating painful venous malformations. Participants will receive a daily dose of enalapril, starting at 5 mg, which may be increased to 10 mg if necessary, over a treatment period of 12 months. The study aims to assess whether enalapril can reduce pain and the volume of the malformation, thereby improving the quality of life for patients. Follow-up visits will occur at regular intervals to monitor progress and outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with clinically verified venous malformations that cause significant pain affecting daily activities.

Not a fit: Patients without painful venous malformations or those whose pain does not significantly impact their quality of life may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly alleviate pain and improve the quality of life for patients suffering from venous malformations.

How similar studies have performed: While this approach is novel, previous observations suggest potential benefits of ACE inhibitors in similar conditions, warranting further investigation.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. 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.
3. Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
4. 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.
5. 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)
6. 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.

Exclusion Criteria:

1. Diffuse VM with no defined borders.
2. Known diabetes because of the risk of hypoglycemia.
3. Impaired liver function (INR \> 1,5 or aminotransferases \> 3 times upper limit of normal
4. Use of mTOR-inhibitor, racekadotril, sacubitril/valsartan, ramipril or vildagliptin is contraindicated because of an elevated risk of angioedema
5. Use of angiotensin-II receptor antagonist or alsikiren (direct renin inhibitor) is contraindicated because of increased risk of hypotension, hyperkalemia, and impaired renal function.
6. Impaired cardiac function and clinically significant cardiac disease including aorta- and mitral valve stenosis and hypertrophic cardiomyopathy.
7. Lactose intolerance, total lactase deficiency or glucose-galactose malabsorption because Enalapril contains lactose.
8. 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.)
9. 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.
10. Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicated participation in the clinical study.
11. Known renal artery stenosis.
12. Patients with a history of angioneurotic edema related to previous treatment with ACE-inhibitors and patients with Hereditary or ideopatic anigioneurotic edema.
13. Contraindications for MRI (cardiac pacemaker or defibrillator, intracranial clips, cochlear implants or other metallic foreign bodies, claustrophobia.
14. BMI\> 30
15. Impaired kidney function (eGFR\< 50)
16. Pregnant or lactating woman
17. Any condition that in the view of the investigator would suggest that the patient is unable to compley with the study protocol and procedures.

Where this trial is running

Oslo, Norway

• Oslo University Hospital, Rikshospitalet — Oslo, Norway, Norway (RECRUITING)

Study contacts

• Study coordinator: Christina Bjerring Opheim, MD and PhD student

Conditions: Venous Malformation, Pain, Quality of Life, Vascular Malformation