Cardiorenal Syndrome, Chronic Kidney Disease
Conditions
Brief summary
The goal of this trial is to evaluate whether subantimicrobial-dose of doxycycline (20mgBID) will affect serum and urine biomarkers of fibrosis in patients with pre-dialysis chronic kidney disease.
Detailed description
This is a Phase I, placebo-controlled, randomized crossover trial to determine the effects of 4-week treatment with subantimicrobial-dose doxycycline on serum and urine biomarkers of fibrosis in patients with pre-dialysis chronic kidney disease (eGFR\<30ml/min/1.73m2). Doxycycline is a matrix metalloproteinase inhibitor and is approved for use as an anti-fibrotic in the setting of gum and skin disease at low doses (20mgBID). At such a dose, serum levels are too low for antimicrobial effect and chronic usage is not thought to lead to tetracycline resistance. Investigators hypothesize that doxycycline will ameliorate cardiac and renal fibrosis and thus investigators will detect a decrease in fibrotic markers during treatment with doxycycline.
Interventions
DRUGDoxycycline
Doxycycline 20mg capsule by mouth, twice a day for 30 days.
DRUGPlacebo (for Doxycycline)
Inactive pill manufactured to mimic Doxycycline 20mg. Capsule by mouth, twice a for 30 days.
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CKD pre-dialysis (eGFR\< 30 ml/min/1.73m2 not on dialysis); * local 415/650/510 area codes; * primary language English or Spanish
Exclusion criteria
* eGFR worsening by greater than 5ml/min/1.73 m2 during the last 6 months; * Systolic blood pressure less than 100mmHg or greater than 170 mmHg; * pregnancy; * ejection fraction less than 45%; * NYHA class III or IV HF; * myocardial infarction or hospitalization for HF within 4 months; * liver disease; * moderate or severe chronic obstructive pulmonary disease or pulmonary fibrosis; * current infection; * chemotherapy; * major surgery within last month; * bilateral dialysis access precluding lab draw; * self-reported use of IV drugs or cocaine within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum markers of fibrosis | 3 months | Serum collagen type III amino-terminal propeptide (PIIINP), soluble suppression of tumorigenicity 2 (ST2) |
| Urinary markers of fibrosis | 3 months | Urinary PIIINP, Urinary alpha-1 macroglobulin (A1M) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse effects | 3 months | Nausea, rash |
Countries
United States
Outcome results
None listed