A Trial of Doxycycline in Renal Disease (ADORE)

A Trial of Doxycycline in Renal Disease (ADORE)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Cardiorenal Syndrome
• Intervention / Treatment: Drug: Doxycycline; Drug: Placebo (for Doxycycline)

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Ruth Dubin, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: April 24, 2016
• First Submitted That Met QC Criteria: April 26, 2016
• First Posted (Estimate): April 27, 2016

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Renal Insufficiency; Heart Failure; Kidney Diseases; Renal Insufficiency, Chronic; Cardio-Renal Syndrome; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 15-17569

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No