A Trial of Doxycycline in Renal Disease

Phase 1

Completed

• Conditions: Cardiorenal Syndrome; Chronic Kidney Disease
• Interventions: Drug: Doxycycline; Drug: Placebo (for Doxycycline)

• Registration Number: NCT02753426
• Lead Sponsor: University of California, San Francisco

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.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-04-24
• Study First Submitted QC: 2016-04-26
• Study First Posted: 2016-04-27
• Primary Completion: 2017-12
• Study Completion: 2018-01
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-05
• Last Update Posted: 2020-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Doxycycline-Placebo	Placebo (for Doxycycline)	Doxycycline 20mg capsule for 30 days, 30-day washout, and then placebo capsule for 30 days.
Placebo-Doxycycline	Placebo (for Doxycycline)	Placebo capsule for 30 days, 30-day washout, and then Doxycycline 20mg capsule for 30 days.
Doxycycline-Placebo	Doxycycline	Doxycycline 20mg capsule for 30 days, 30-day washout, and then placebo capsule for 30 days.
Placebo-Doxycycline	Doxycycline	Placebo capsule for 30 days, 30-day washout, and then Doxycycline 20mg capsule for 30 days.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Adverse effects	3 months	Nausea, rash

Trial Locations

Locations (1)

Zuckerberg San Francisco General Hospital; 🇺🇸 San Francisco, California, United States