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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor

Conditions
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Type 2 Diabetes, Obesity

Intervention / Treatment
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* Drug: Doxycycline
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxycycline<br>Participants with DM2 receiving doxycycline 100mg BID | Drug: Doxycycline<br>* generic doxycycline 100mg twice daily<br>* Other names: Vibramycin;|
| Placebo Comparator: Placebo<br>Pills prepared identical to doxycycline. | Other: Placebo<br>* Placebo comparator to doxycycline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMP Activity | MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9. | Baseline (Day 1) | 
| MMP Activity | 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. | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRP | Measure of global inflammation. | Baseline (Day 1) | 
| CRP | Measure of global inflammation. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84. | Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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doxycycline, insulin resistance, obesity, inflammation