Obesity
Conditions
Keywords
Plasma PAI-1 level at 0, 4, 8 weeks, Plasma hsCRP level at 0, 4, 8 weeks, Plasma TNF-a level at 0, 4, 8 weeks
Brief summary
PAI-1 is elevated in obese individuals. TNF-alpha, an inflammatory mediator is believed to play a role in obesity mediated elevations in PAI-1 levels. TNF-alpha blockade with antibodies and the drug pentoxifylline have been shown to lower PAI-1 levels in animal models. This study tests the hypothesis that pentoxifylline will lower PAI-1 levels in human subjects.
Detailed description
Obese individuals with elevated PAI-1 levels (greater than 10 ng/ml) are randomized to pentoxifylline 400mg, three times a day (TID) or placebo for 8 weeks. PAI-1, TNF-a and high sensitivity C-Reactive Protein are measured at week 0, 4 and 8.
Interventions
DRUGPentoxifylline
400mg PO TID x 8 weeks
DRUGPlacebo
PO TID x 8 weeks
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusions: 1. A Body Mass Index of ≥ 30.0 2. Age 21 or older 3. Few or no medical problems 4. PAI-1 level ≥ 10 ng/dl Exclusions: 1. Cigarette use 2. Present use of angiotensin converting enzyme (ACE) Inhibitors 3. Recent cerebral and/or retinal hemorrhage 4. Intolerance to pentoxifylline or methylxanthines such as caffeine, theophylline, and theobromine 5. Presently on warfarin therapy 6. Pregnancy or breast-feeding 7. Recent surgery 8. Recent diagnosis/treatment for peptic ulcer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in PAI-1 Level | Baseline and 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in CRP Level | Baseline and 8 weeks |
| Change in TNF-alpha Level | Baseline and 8 weeks |
| Changes in the Relationship Between PAI-1, CRP, and TNF-a With Therapy. | Baseline and 8 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pentoxifylline Patients receive Pentoxifylline 400 mg po TID for 8 weeks.
Pentoxifylline: 400mg PO TID x 8 weeks | 22 |
| Placebo Patients take a placebo TID for 8 weeks.
Placebo: PO TID x 8 weeks | 15 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | Pentoxifylline | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 3.1 | 38.6 years STANDARD_DEVIATION 2.5 | 38.2 years STANDARD_DEVIATION 1.9 |
| Region of Enrollment United States | 22 participants | 15 participants | 37 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 22 | 2 / 15 |
| serious Total, serious adverse events | 0 / 22 | 0 / 15 |
Outcome results
Primary
Change in PAI-1 Level
Time frame: Baseline and 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pentoxifylline | Change in PAI-1 Level | Baseline | 39.5 ng/ml | Standard Error 8.3 |
| Pentoxifylline | Change in PAI-1 Level | 8 Weeks | 28.6 ng/ml | Standard Error 7.7 |
| Placebo | Change in PAI-1 Level | Baseline | 31.6 ng/ml | Standard Error 7.6 |
| Placebo | Change in PAI-1 Level | 8 Weeks | 37.9 ng/ml | Standard Error 8.5 |
p-value: 0.0005Wilcoxon (Mann-Whitney)
Secondary
Change in CRP Level
Time frame: Baseline and 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pentoxifylline | Change in CRP Level | Baseline | 5.2 mg/dl | Standard Error 2.5 |
| Pentoxifylline | Change in CRP Level | 8 weeks | 4.6 mg/dl | Standard Error 1.9 |
| Placebo | Change in CRP Level | Baseline | 2.9 mg/dl | Standard Error 0.5 |
| Placebo | Change in CRP Level | 8 weeks | 2.4 mg/dl | Standard Error 0.5 |
p-value: 0.0114Wilcoxon (Mann-Whitney)
Secondary
Change in TNF-alpha Level
Time frame: Baseline and 8 weeks
Population: TNF-a assay did not work properly. Meaningless data resulted including negative values which are impossible.
Secondary
Changes in the Relationship Between PAI-1, CRP, and TNF-a With Therapy.
Time frame: Baseline and 8 weeks
Population: Unable to complete analysis due to TNF-a assay failure (see Outcome measure #3)