To investigate the effect of a medicine called doxycycline in people with evidence of stiffening of the heart muscle

• Conditions: MedDRA version: 14.1Level: PTClassification code 10052337Term: Diastolic dysfunctionSystem Organ Class: 10007541 - Cardiac disorders; Diastolic dysfunction; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-021664-16-IE
• Lead Sponsor: Solvotrin Innovations Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-06
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Treated for hypertension > 6 months

Doppler-echocardiographic evidence of severe diastolic dysfunction (see Echo Doppler investigation below)

Clinically stable (on same treatment for > 1 month)

Informed consent

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.Age < 18 years at the time of randomisation

2.Tetracycline allergy

3.Pre-menopausal women (defined as last menstrual period <12 months earlier) (ie postmenopausal women only will be eligible for enrolment. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.

4.Prior documented LVEF <45% or qualitative moderate or severe LV systolic dysfunction

5.Change in diuretics within 1 month or recent admission for acute decompensated heart failure/ cardiovascular event (eg ischemia) < 3 months

6.Haemodynamically severe valvular heart disease

7.Evidence of significant inflammatory disease, connective tissue disease, hepatic disease, metabolic bone disease which may alter parameters of collagen metabolism

8.Hypertrophic, restrictive or constrictive cardiomyopathy

9.Clinically significant pulmonary disease as evidenced by hospitalisations or use of oral corticosteroids for pulmonary decompensation within 12 months, or requirement for home O2 or significant fibrosis

10.Severe anaemia (Haemoglobin <8.0g/dL)

11.Severe renal dysfunction (GFR < 30 mL/min/1.73m2)

The estimated GFR (eGFR) will be calculated by the following MDRD equation:

eGFR (ml/min/1.73m2) = 186 (serum creatinine mg/dL)1.154 X (age)0.203 X (0.742 if subject is female) X (1.210 if subject is African American).

12.Subjects with hepatic dysfunction (one or more LFTs greater than three times the upper limit of normal)

13.Gastro-oesophageal reflux disease

14.Recent trauma or surgery (<6 months)

15.Malignancy

16.Subjects with contraindications to MRI
a.Hypersensitivity to gadolinium containing contrast agents
b.Brain Aneurysm Clip
c.Implanted neural stimulator
d.Implanted cardiac pacemaker or defibrillator
e.Cochlear implant
f.Ocular foreign body (e.g. metal shavings)
g.Other implanted medical devices: (e.g. Swan Ganz catheter)
h.Insulin pump
i.Metal shrapnel or bullet.

17.Contraindications to doxycycline therapy:

a.Use in subjects with hypersensitivity to tetracyclines
b.Use during pregnancy or breast feeding
c.Obstructive oesophageal disorders such as stricture or achalasia.

18.Subjects on cyclosporin.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the impact of doxycyline on MMP-2, MMP-9 and other markers of collagen turnover in patients with severe diastolic dysfunction and hypertensive heart disease<br>;Secondary Objective: To assess the impact of doxycycline on Doppler-echocardiographic parameters of diastolic dysfunction.<br><br>To determine whether the impact of doxycycline on markers of collagen turnover in the aforementioned patients is associated with cardiac structural and functional changes on cardiac MRI.<br>;Primary end point(s): The primary end point of this study is the difference in plasma levels of MMP-2 and MMP-9 and other markers of collagen turnover in patients with severe diastolic dysfunction and hypertensive heart disease.;Timepoint(s) of evaluation of this end point: Baseline (Time 0), 2 weeks, 4 weeks, 6 months and 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To assess the impact of doxycycline on Doppler Echocardiography parameters of diastolic dysfunction.<br><br>To determine whether the impact of doxycycline on markers of collagen turnover in the aforementioned patients is associated with cardiac structural and functional changes on cardiac MRI.<br>;Timepoint(s) of evaluation of this end point: Baseline (Time 0), six months and 12 months