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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxycycline-Placebo | Other | Doxycycline 20mg capsule for 30 days, 30-day washout, and then placebo capsule for 30 days. |
|
| Placebo-Doxycycline | Other | Placebo capsule for 30 days, 30-day washout, and then Doxycycline 20mg capsule for 30 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxycycline | Drug | Doxycycline 20mg capsule by mouth, twice a day for 30 days. |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse effects | Nausea, rash | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ruth Dubin, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zuckerberg San Francisco General Hospital | San Francisco | California | 94110 | United States |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D059347 | Cardio-Renal Syndrome |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D004318 | Doxycycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Placebo (for Doxycycline) | Drug | Inactive pill manufactured to mimic Doxycycline 20mg. Capsule by mouth, twice a for 30 days. |
|
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006333 | Heart Failure |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |