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

NCT01375491 | Completed Phase 4 Results

• 3 other identifiers: 0903955M01RR000827P30DK063491
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 2 Diabetes; Obesity

Keywords

doxycycline; insulin resistance; obesity; inflammation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• CRP

  Baseline (Day 1)

• CRP

  Day 84

Study Arms (2)

Doxycycline

EXPERIMENTAL

Participants with DM2 receiving doxycycline 100mg BID

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

Pills prepared identical to doxycycline.

Other: Placebo

Interventions

Doxycycline DRUG

generic doxycycline 100mg twice daily

Also known as: Vibramycin

Doxycycline

Placebo OTHER

Placebo comparator to doxycycline

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• % \< HA1C \< 10%
• Taking insulin and/or oral medications (biguanide, sulfonlylurea, etc.)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of California, San Diego: lead
• Ruth L. Kirschstein National Research Service Award: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

University of California San Diego Clinical trials Research Institute

La Jolla, California, 92093, United States

Location

Related Publications (2)

• 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.

  PMID: 18606910 BACKGROUND

• 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.

  PMID: 23025537 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Insulin Resistance; Inflammation

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Pathologic Processes

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

This information is being entered from a publication, since the Principal Investigator is no longer associated with the institution. The publication does not report on adverse events and so there is no way to report these numbers.

Results Point of Contact

• Title: Dr. Karen Louise Herbst
• Organization: University of California, San Diego

kaherbst@gmail.com

858-552-8585

Study Officials

• Karen L Herbst, PhD, MD

  UCSD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2011
• First Posted: June 17, 2011
• Study Start: October 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: January 13, 2020
• Results First Posted: January 13, 2020

Record last verified: 2020-01

Locations

US (1)