Obesity, Type 2 Diabetes
Conditions
Keywords
doxycycline, insulin resistance, obesity, inflammation
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.
Interventions
DRUGDoxycycline
generic doxycycline 100mg twice daily
OTHERPlacebo
Placebo comparator to doxycycline
Sponsors
Ruth L. Kirschstein National Research Service Award
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Research Resources (NCRR)
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MMP Activity | Baseline (Day 1) | MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CRP | Baseline (Day 1) | Measure of global inflammation. |
Countries
United States
Participant flow
Recruitment details
The study included non-type 2 diabetics controls (n = 15), and type two diabetics subjects randomized to placebo (n = 13) or doxycycline 100 mg twice daily (n = 11).
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline Participants with DM2 receiving doxycycline 100mg BID
Doxycycline : generic doxycycline 100mg twice daily | 11 |
| Placebo Pills prepared identical to doxycycline.
Placebo : Placebo comparator to doxycycline | 13 |
| Control Participants enrolled without type 2 diabetes to serve as a control | 15 |
| Total | 39 |
Baseline characteristics
| Characteristic | Doxycycline | Placebo | Control | Total |
|---|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 1.9 | 54.5 years STANDARD_DEVIATION 1.7 | 48.7 years STANDARD_DEVIATION 3.1 | 54.9 years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
MMP Activity
MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9.
Time frame: Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | MMP Activity | 56.8 uM 5-FAM/h-ug protein | Standard Error 13.3 |
| Placebo | MMP Activity | 43.8 uM 5-FAM/h-ug protein | Standard Error 4 |
| Control Arm | MMP Activity | 47.2 uM 5-FAM/h-ug protein | Standard Error 3.2 |
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.
Time frame: Day 84
Population: Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | MMP Activity | 59.7 uM 5-FAM/h-ug protein | Standard Error 4.3 |
| Placebo | MMP Activity | 56.6 uM 5-FAM/h-ug protein | Standard Error 10.1 |
Secondary
CRP
Measure of global inflammation.
Time frame: Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | CRP | 7.4 microgram/ml | Standard Error 3.3 |
| Placebo | CRP | 5.9 microgram/ml | Standard Error 1.8 |
| Control Arm | CRP | 1.9 microgram/ml | Standard Error 0.8 |
Comparison: See published paper.p-value: <0.05ANOVA
Secondary
CRP
Measure of global inflammation. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.
Time frame: Day 84
Population: Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | CRP | 2.3 microgram/ml | Standard Error 0.4 |
| Placebo | CRP | 6.2 microgram/ml | Standard Error 1.8 |