Clinical trial NCT01375491: Examination of the Anti-inflammatory and Insulin Sensitizing Properties of Doxycycline in Humans
Official title: Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Obesity
Keywords: doxycycline
insulin resistance
obesity
inflammation
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Ruth L. Kirschstein National Research Service Award
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
First posted: 2011-06-17
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: MMP Activity
timeFrame: Baseline (Day 1)
measure: MMP Activity
timeFrame: Day 84
Secondary outcomes:
measure: CRP
timeFrame: Baseline (Day 1)
measure: CRP
timeFrame: Day 84
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Clinical trials Research Institute
state: California
Study officials:
affiliation: UCSD
name: Karen L Herbst, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: DeLano FA, Schmid-Schonbein 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.
citation: Frankwich K, Tibble C, Torres-Gonzalez M, Bonner M, Lefkowitz R, Tyndall M, Schmid-Schonbein GW, Villarreal F, Heller M, Herbst K. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes. J Inflamm (Lond). 2012 Oct 1;9(1):35. doi: 10.1186/1476-9255-9-35.