Diastolic dysfunction MedDRA version: 14.1 Level: PT Classification code 10052337 Term: Diastolic dysfunction System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: By-Mycin 50mg capsules
Product Name: Doxycycline
Product Code: NA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Doxycycline Hyclate
CAS Number: 24390-14-5
Current Sponsor code: N
Sponsors
Solvotrin Innovations Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 ;Secondary Objective: To assess the impact of doxycycline on Doppler-echocardiographic parameters of diastolic dysfunction. 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. ;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the impact of doxycycline on Doppler Echocardiography parameters of diastolic dysfunction. 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. ;Timepoint(s) of evaluation of this end point: Baseline (Time 0), six months and 12 months | — |
Countries
Ireland
Contacts
Public ContactClinical Trials Information
Solvotrin Innovations
Outcome results
None listed