Examination of the Anti-inflammatory and Insulin Sensitizing Properties of Doxycycline in Humans

Phase 4

Completed

• Conditions: Type 2 Diabetes; Obesity
• Interventions: Other: Placebo; Drug: Doxycycline

• Registration Number: NCT01375491
• Lead Sponsor: University of California, San Diego

Brief Summary

Obesity is a heightened state of inflammation in which production of cytokines and matrix metalloproteinases (MMPs) result in loss of function of insulin receptors and insulin resistance. Doxycycline (DOX) is a potent MMP inhibitor. We hypothesize that DOX will enhance insulin sensitivity and decreases inflammation in obese participants with type 2 diabetes (DM2).

Detailed Description

Design and Setting: 84 day (D84), double-blind, randomized, placebo (PL)-controlled clinical trial conducted in an academic tertiary care center.

Patients: Non-DM2 Controls (n=15); participants with DM2 receiving PL (n=13) or DOX (n=11).

Interventions: All participants were evaluated at day 1 (D1); those with DM2 were also evaluated at D84 after DOX 100mg twice daily or PL.

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2011-05-25
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Study First Submitted QC: 2011-06-16
• Study First Posted: 2011-06-17
• Results First Submitted: 2019-12-05
• Status Verified: 2020-01
• Results First Submitted QC: 2020-01-08
• Last Update Submitted: 2020-01-08
• Results First Posted: 2020-01-13
• Last Update Posted: 2020-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• Ambulatory, medically stable, able to give informed consent, and comply with the protocol.
• Obesity with BMI >30 kg/m2.
• DM2 for less than 10 years.
• 7.5% < HA1C < 10%
• Taking insulin and/or oral medications (biguanide, sulfonlylurea, etc.)

Exclusion Criteria

• Mental states that would preclude complete understanding of the protocol and compliance.
• Chronic illness such as renal failure (with creatinine clearance <80 ml/min for Specific Aim 2).
• Women of child-bearing age because of the potential hazard to the fetus (doxycycline may cause permanent discoloration of the teeth and deposition in bone inhibiting growth) and because doxycycline may render oral contraceptives less effective.
• Nursing mothers.
• Allergy to tetracyclines.
• Subjects taking the following drugs: penicillin or it's derivatives, anticoagulant therapy, antacids containing aluminum, calcium, or magnesium, iron-containing preparations, bismuth subsalicylate, barbiturates, carbamazepine, phenytoin or methoxyflurane, thiazolidinediones (TZD)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Pills prepared identical to doxycycline.
Doxycycline	Doxycycline	Participants with DM2 receiving doxycycline 100mg BID

Primary Outcome Measures

Name	Time	Method
MMP Activity	Day 84	MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.

Secondary Outcome Measures

Name	Time	Method
CRP	Day 84	Measure of global inflammation. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.

Trial Locations

Locations (1)

University of California San Diego Clinical trials Research Institute; 🇺🇸 La Jolla, California, United States