A pilot study of enalapril in venous malformations

Phase 1

• Conditions: Venous malformation; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: CTIS2023-510076-31-00
• Lead Sponsor: Oslo University Hospital HF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-27
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

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, interferes with sleep and 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. Highly effective birth control methods include: ?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.

Exclusion Criteria

Diffuse VM with no defined borders., 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., 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 the SmPC of enalpril or to other ACE-inhibitors., Patients with a history of angioneurotic edema related to previous treatment with ACE-inhibitors and patients with Hereditary or ideopatic anigioneurotic edema, 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, BMI > 30, Impaired renal function (eGFR < 50 ml/min/1,73m2), Pregnant or lactating woman, Any condition that in the view of the investigator would suggest that the patient is unable to comply with the study protocol and procedures., Known diabetes because of the risk of hypoglycemia., Chronic liver failure

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To explore the change of VM related pain.;Secondary Objective: To explore volume change of the VM, To explore change in quality of life in patients with VM, To investigate safety in patients with VM;Primary end point(s): Change in NRS score 12 months after treatment start with enalapril compared to baseline.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Volume change on MRI 12 months after treatment start with enalapril compared to baseline.;Secondary end point(s):Change in Quality of life 12 months after treatment start with enalapril compared to baseline.;Secondary end point(s):Register adverse events and side effects continues during the study