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

Obesity Clinical Trial

— DOXY  

Official title:

Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01375491
• Other study ID #: 090395
• Secondary ID: 5M01RR000827P30D
• Status: Completed
• Phase: Phase 4
• Start date: October 2009
• Est. completion date: June 2011

Study information

• Verified date: January 2020
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Obesity
• Type 2 Diabetes

Intervention

Drug:
• Doxycycline
generic doxycycline 100mg twice daily

Other:
• Placebo
Placebo comparator to doxycycline

Locations

Country	Name	City	State
United States	University of California San Diego Clinical trials Research Institute	La Jolla	California

Sponsors (4)

Lead Sponsor	Collaborator
University of California, San Diego	National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Ruth L. Kirschstein National Research Service Award

Country where clinical trial is conducted

United States, 

References & Publications (2)

DeLano FA, Schmid-Schönbein GW. Proteinase activity and receptor cleavage: mechanism for insulin resistance in the spontaneously hypertensive rat. Hypertension. 2008 Aug;52(2):415-23. doi: 10.1161/HYPERTENSIONAHA.107.104356. Epub 2008 Jul 7. — View Citation

Frankwich K, Tibble C, Torres-Gonzalez M, Bonner M, Lefkowitz R, Tyndall M, Schmid-Schönbein GW, Villarreal F, Heller M, Herbst K. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in peopl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MMP Activity	MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9.	Baseline (Day 1)
Primary	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	CRP	Measure of global inflammation.	Baseline (Day 1)
Secondary	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