Marfan SyndromePhase 2NCT01949233
The Oxford Marfan Trial
A Phase 2 study testing Irbesartan 150-300mg capsules daily for 6 months and Doxycycline 100-200mg capsules daily for 6 months in people with Marfan Syndrome, run by University of Oxford at 2 sites in United Kingdom.
Trial summary
The primary objective of the trial is to estimate the effects of allocation to irbesartan, or doxycycline, or a combination of both irbesartan and doxycycline, compared with placebo, on measures of elastic function of the aorta in people with the Marfan syndrome and enlargement of the aorta. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Marfan Syndrome
- What is being tested?
- Irbesartan 150-300mg capsules daily for 6 months and Doxycycline 100-200mg capsules daily for 6 months
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Oct 2013to Dec 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, aged 13 years or above at last birthday (note that there is no upper age limit for inclusion in this trial)
- For those aged greater than or equal to 16 years of age at the time of enrolment, participant is willing and, in the opinion of the investigator, able to give informed consent for participation in the trial
- For those aged 13-15 at the time of enrolment, participant is willing and, in the opinion of the investigator, able to give informed assent, and parent/guardian is willing and able to give informed consent for participation in the trial.
- Weight ≥ 50kg
- Diagnosed with Marfan syndrome according to the revised Ghent criteria 1996
- Dilated aorta (BSA-adjusted aortic root z-score ≥2 at the aortic sinuses of Valsalva, using the method of Roman et al, or an absolute aortic root dimension >4.0cm at the sinuses of Valsalva measured using either echocardiography or CMR)
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- If the participant is a female of child-bearing potential, they are willing to ensure effective contraception as defined in the contraception policy
- If the participant is taking β-blocker therapy, they are willing to stop taking these one week prior to each CMR scan
- Willing and, in the investigator's opinion, able to comply with all trial requirements
- Willing to allow his or her General Practitioner and if appropriate, Consultant, to be informed of his or her participation in the trial and of any clinical findings or issues which may arise
Who cannot join
- Female who is pregnant
- Female who is planning pregnancy within 6 months of enrolment
- Female who is breast feeding
- Previous aortic dissection
- Previous aortic surgery
- Bicuspid or unicuspid aortic valve
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- Scheduled elective cardiac or aortic surgery within 6 months of enrolment
- Definite diagnosis of Loeys-Dietz or Shpritzen-Goldberg syndrome
- Known bilateral renal artery stenosis or renal artery stenosis to a single functioning kidney
- History of idiopathic intracranial hypertension
- Exposure to angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, or medications containing these compounds in the 3 months prior to enrolment in the trial
- Absolute indication for angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, doxycycline or other antibiotics of the tetracycline class at enrolment
- Taking β-blocker therapy for an indication other than the Marfan syndrome
- Participant has participated in another research study involving an investigational medicinal product or device in the 3 months prior to enrolment
- Renal impairment of a moderate or severe degree (eGFR <60 mls/min/1.73m2)
- Hyperkalaemia (>5.1 mmol/L)
- Significant hepatic impairment (ALT or AST >3 times upper limit of normal)
- History of allergic reaction or any other clinically significant intolerance to irbesartan or its constituents; other angiotensin receptor blockers / antagonists; angiotensin converting enzyme inhibitors, doxycycline or its constituents, or placebo medications or its constituents
- Contra-indications to MRI (e.g. implantable cardiac electronic device, claustrophobia, intracranial aneurysm clips and metallic ocular foreign bodies etc.)
- Participant currently required to take or likely to be required to start, in the 6 months following enrolment, a medicinal product which is known or suspected to interact, to a clinically significant extent, with irbesartan including: potassium supplementation, potassium sparing diuretics, lithium, regular use of antacids containing aluminium magnesium hydroxide
- Participant currently required to take or likely to be required to start, in the 6 months following enrolment, a medicinal product which is known or suspected to interact, to a clinically significant extent, with doxycycline including ergotamine and methysergide. This includes drugs known to induce the cytochrome P450 system to a clinically significant extent, including but not limited to, carbamazepine, phenytoin, rifampicin, griseofulvin, barbiturates or sulphonylureas.
- Alcohol dependence
- Any other significant disease, disorder or circumstance (e.g. terminal illness), which, in the opinion of the Investigator, may either put the participant at risk in the trial, or may introduce significant bias to the trial, or may affect the participant's ability to participate in the trial
Trial locations and contacts
2 sites in 1 country.
Hayley Harvey contact
Alex Pitcher, MA (Oxon),DPhil, BM Mch, MRCP contact
United Kingdom2 sites, 2 recruiting
- Recruiting
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Edward Blair, MBChB MRCP
Paul Wordsworth, MB FRCP
- Recruiting
University of Oxford
Oxford, Oxfordshire, OX3 9DU
Alex Pitcher, DPhil, MA, BM BCh, MRCP
Andrew Lewis, MB BS MRes MRCP
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Pilot Trial of Irbesartan, Doxycycline and a Combination on Markers of Vascular Dysfunction in the Marfan Syndrome, Using Cardiovascular Magnetic Resonance Imaging
The primary objective of the trial is to estimate the effects of allocation to irbesartan, or doxycycline, or a combination of both irbesartan and doxycycline, compared with placebo, on measures of elastic function of the aorta in people with the Marfan syndrome and enlargement of the aorta.
- Conditions
- Marfan Syndrome
- Being tested
- Irbesartan 150-300mg capsules daily for 6 months, Doxycycline 100-200mg capsules daily for 6 months, Doxycycline placebo capsules daily for 6 months, Irbesartan placebo capsules daily for 6 months
- Medical subject headings
- Marfan Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irbesartan 150-300mg capsules daily for 6 monthsDrug
Doxycycline 100-200mg capsules daily for 6 monthsDrug
Doxycycline placebo capsules daily for 6 monthsDrug
Irbesartan placebo capsules daily for 6 monthsDrug
| Study group | Role | What they receive |
|---|---|---|
| Irbesartan 150-300mg (and doxycycline placebo) | Experimental | Irbesartan 150-300mg capsules daily for 6 months Doxycycline placebo capsules daily for 6 months Receives: Drug: Irbesartan 150-300mg capsules daily for 6 months; Drug: Doxycycline placebo capsules daily for 6 months |
| Doxycycline 100-200mg (and irbesartan placebo) | Experimental | Doxycycline 100-200mg capsules daily for 6 months Irbesartan placebo capsules daily for 6 months Receives: Drug: Doxycycline 100-200mg capsules daily for 6 months; Drug: Irbesartan placebo capsules daily for 6 months |
| Irbesartan 150-300mg and doxycycline 100-200mg | Experimental | Irbesartan 150-300mg capsules daily for 6 months Doxycycline 100-200mg capsules daily for 6 months Receives: Drug: Irbesartan 150-300mg capsules daily for 6 months; Drug: Doxycycline 100-200mg capsules daily for 6 months |
| irbesartan and doxycycline placebo | Placebo comparator | Irbesartan placebo capsules daily for 6 months Doxycycline placebo capsules daily for 6 months Receives: Drug: Doxycycline placebo capsules daily for 6 months; Drug: Irbesartan placebo capsules daily for 6 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change (i.e. difference between first and last study visits) in aortic distensibility in the ascending aorta between allocation arms measured using CMR
Measured: 0 months and 6 months
Secondary outcomes (11)
1. Change in aortic distensibility in the proximal and distal descending aorta between allocation arms measured using CMR
Measured: 0 and 6 months
2. Change in aortic dimensions in the proximal and distal descending aorta
Measured: 0 and 6 months
3. Change in mean and peak axial and mean and peak circumferential aortic wall shear stress between allocation arms estimated by CMR using a 4D flow sequence
Measured: 0 and 6 months
4. Change in peripheral (brachial) blood pressure between allocation arms measured using a calibrated, validated automated sphygmomanometer
Measured: 0 and 6 months
5. Change in central blood pressure, and augmentation index between allocation arms measured by applanation tonometry and by oscillometric sphygmomanometry
Measured: 0 and 6 months
6. Change in left ventricular volumes, mass and systolic function between allocation arms to placebo measured by CMR
Measured: 0 and 6 months
7. Change in aortic pulse wave velocity between allocation arms measured by CMR
Measured: 0 and 6 months
8. Change in carotid-femoral pulse wave velocity between allocation arms compared to placebo measured by applanation tonometry
Measured: 0 and 6 months
9. Change in TGF-β level, or other biomarker, between allocation arms compared to placebo
Measured: 0 and 6 months
10. Tolerability and safety of irbesartan and doxycycline, assessed by incidence of adverse reactions and change in health status score, using the SF-36 questionnaire
Measured: 0, 0.5 and 6 months
11. Document the frequency of aortic dissection, death from cardiovascular causes, or need for aortic root or valve surgery (if any) in each allocation arm
Measured: 0-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2015 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Marfan SyndromeStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Oxford University Hospitals NHS Trust
- Responsible party
- Sponsor
- Investigators
- J Colin Forfar, BSc (hons), MA(Oxon), MD, PhD,, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01949233
- Sponsor's protocol ID
- 2010-023612-14
- Status last verified
- Jun 2015
- First submitted
- 6 Aug 2013
- Last updated
- 9 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Pilot Trial of Irbesartan, Doxycycline and a Combination on Markers of Vascular Dysfunction in the Marfan Syndrome, Using Cardiovascular Magnetic Resonance Imaging
- ClinicalTrials.gov ID
- NCT01949233
- Acronym / sponsor ID
- 2010-023612-14
- Conditions
- Marfan Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Oxford University Hospitals NHS Trust
- Study start
- Oct 2013
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 24 Sep 2013 (estimated)
- 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 primary objective of the trial is to estimate the effects of allocation to irbesartan, or doxycycline, or a combination of both irbesartan and doxycycline, compared with placebo, on measures of elastic function of the aorta in people with the Marfan syndrome and enlargement of the aorta.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Irbesartan 150-300mg (and doxycycline placebo) | Experimental | Drug: Irbesartan 150-300mg capsules daily for 6 months, Drug: Doxycycline placebo capsules daily for 6 monthsIrbesartan 150-300mg capsules daily for 6 months Doxycycline placebo capsules daily for 6 months |
| Doxycycline 100-200mg (and irbesartan placebo) | Experimental | Drug: Doxycycline 100-200mg capsules daily for 6 months, Drug: Irbesartan placebo capsules daily for 6 monthsDoxycycline 100-200mg capsules daily for 6 months Irbesartan placebo capsules daily for 6 months |
| Irbesartan 150-300mg and doxycycline 100-200mg | Experimental | Drug: Irbesartan 150-300mg capsules daily for 6 months, Drug: Doxycycline 100-200mg capsules daily for 6 monthsIrbesartan 150-300mg capsules daily for 6 months Doxycycline 100-200mg capsules daily for 6 months |
| irbesartan and doxycycline placebo | Placebo comparator | Drug: Doxycycline placebo capsules daily for 6 months, Drug: Irbesartan placebo capsules daily for 6 monthsIrbesartan placebo capsules daily for 6 months Doxycycline placebo capsules daily for 6 months |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female, aged 13 years or above at last birthday (note that there is no upper age limit for inclusion in this trial)
- For those aged greater than or equal to 16 years of age at the time of enrolment, participant is willing and, in the opinion of the investigator, able to give informed consent for participation in the trial
- For those aged 13-15 at the time of enrolment, participant is willing and, in the opinion of the investigator, able to give informed assent, and parent/guardian is willing and able to give informed consent for participation in the trial.
- Weight ≥ 50kg
- Diagnosed with Marfan syndrome according to the revised Ghent criteria 1996
Key exclusion criteria (23 listed)
- Female who is pregnant
- Female who is planning pregnancy within 6 months of enrolment
- Female who is breast feeding
- Previous aortic dissection
- Previous aortic surgery
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 |
|---|---|---|
| Irbesartan 150-300mg capsules daily for 6 months | Drug | Irbesartan 150-300mg (and doxycycline placebo), Irbesartan 150-300mg and doxycycline 100-200mg |
| Doxycycline 100-200mg capsules daily for 6 months | Drug | Doxycycline 100-200mg (and irbesartan placebo), Irbesartan 150-300mg and doxycycline 100-200mg |
| Doxycycline placebo capsules daily for 6 months | Drug | Irbesartan 150-300mg (and doxycycline placebo), irbesartan and doxycycline placebo |
| Irbesartan placebo capsules daily for 6 months | Drug | Doxycycline 100-200mg (and irbesartan placebo), irbesartan and doxycycline placebo |
Primary outcome
Change (i.e. difference between first and last study visits) in aortic distensibility in the ascending aorta between allocation arms measured using CMR
Time frame: 0 months and 6 months
11 secondary outcomes
1. Change in aortic distensibility in the proximal and distal descending aorta between allocation arms measured using CMR
Time frame: 0 and 6 months
2. Change in aortic dimensions in the proximal and distal descending aorta
Time frame: 0 and 6 months
3. Change in mean and peak axial and mean and peak circumferential aortic wall shear stress between allocation arms estimated by CMR using a 4D flow sequence
Time frame: 0 and 6 months
4. Change in peripheral (brachial) blood pressure between allocation arms measured using a calibrated, validated automated sphygmomanometer
Time frame: 0 and 6 months
5. Change in central blood pressure, and augmentation index between allocation arms measured by applanation tonometry and by oscillometric sphygmomanometry
Time frame: 0 and 6 months
6. Change in left ventricular volumes, mass and systolic function between allocation arms to placebo measured by CMR
Time frame: 0 and 6 months
7. Change in aortic pulse wave velocity between allocation arms measured by CMR
Time frame: 0 and 6 months
8. Change in carotid-femoral pulse wave velocity between allocation arms compared to placebo measured by applanation tonometry
Time frame: 0 and 6 months
9. Change in TGF-β level, or other biomarker, between allocation arms compared to placebo
Time frame: 0 and 6 months
10. Tolerability and safety of irbesartan and doxycycline, assessed by incidence of adverse reactions and change in health status score, using the SF-36 questionnaire
Time frame: 0, 0.5 and 6 months
11. Document the frequency of aortic dissection, death from cardiovascular causes, or need for aortic root or valve surgery (if any) in each allocation arm
Time frame: 0-6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2015.
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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.
Hayley Harvey contact
Alex Pitcher, MA (Oxon),DPhil, BM Mch, MRCP contact
J Colin Forfar, BSc (hons), MA(Oxon), MD, PhD, principal investigator
University of Oxford
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irbesartan 150-300mg capsules daily for 6 months and Doxycycline 100-200mg capsules daily for 6 months in people with Marfan Syndrome, run by University of Oxford at 2 sites in United Kingdom.
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 10 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 9 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hayley Harvey (hayley.harvey@cardiov.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change (i.e. difference between first and last study visits) in aortic distensibility in the ascending aorta between allocation arms measured using CMR (time frame: 0 months and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jun 2015; AzTrials last refreshed its copy on 30 Oct 2026.