A Study of Enalapril in Treatment of Venous Malformations

NCT06788314 | Recruiting Phase 2

• 1 other identifier: 2023-510076-31-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Venous Malformation; Pain; Quality of Life; Vascular Malformation

Outcome Measures

Primary Outcomes (1)

• 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.

  From baseline and to the end of treatment at 12 months.

Secondary Outcomes (3)

• To explore volume change of the venous malformation

  From baseline to the end of treatment at 12 months.

• To explore change in quality of life in patients with venous malformations

  From baseline to the end of treatment at 12 months.

• To explore change in quality of life in patients with venous malformations

  From baseline to the end of treatment at 12 months.

Study Arms (1)

Enalapril

EXPERIMENTAL

Drug: Enalapril

Interventions

Enalapril DRUG

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.

Enalapril

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital, Rikshospitalet

Oslo, Norway, Norway

RECRUITING

Related Publications (4)

• 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.

  PMID: 27200356 BACKGROUND

• Tan 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.

  PMID: 29046873 BACKGROUND

• Tan 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.

  PMID: 31321175 BACKGROUND

• Berger 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.

  PMID: 36262918 BACKGROUND

MeSH Terms

Conditions

Pain; Vascular Malformations

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Christina Bjerring Opheim, MD and PhD student

CONTACT

+47 23070000; chbjer@ous-hf.no

Nina Haagenrud Schultz, MD, PhD

CONTACT

+47 23070000; nischu@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor

Model Details: Prospective pilot study

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 23, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: April 2, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)