A Trial of Doxycycline in Renal Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Trial of Doxycycline in Renal Disease (ADORE)

Conditions
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Chronic Kidney Disease, Cardiorenal Syndrome

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Placebo (for Doxycycline)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Doxycycline-Placebo<br>Doxycycline 20mg capsule for 30 days, 30-day washout, and then placebo capsule for 30 days. | Drug: Doxycycline<br>* Doxycycline 20mg capsule by mouth, twice a day for 30 days.<br>Drug: Placebo (for Doxycycline)<br>* Inactive pill manufactured to mimic Doxycycline 20mg. Capsule by mouth, twice a for 30 days.<br>|
| Other: Placebo-Doxycycline<br>Placebo capsule for 30 days, 30-day washout, and then Doxycycline 20mg capsule for 30 days. | Drug: Doxycycline<br>* Doxycycline 20mg capsule by mouth, twice a day for 30 days.<br>Drug: Placebo (for Doxycycline)<br>* Inactive pill manufactured to mimic Doxycycline 20mg. Capsule by mouth, twice a for 30 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum markers of fibrosis | Serum collagen type III amino-terminal propeptide (PIIINP), soluble suppression of tumorigenicity 2 (ST2) | 3 months | 
| Urinary markers of fibrosis | Urinary PIIINP, Urinary alpha-1 macroglobulin (A1M) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects | Nausea, rash | 3 months |