The Effects of Pentoxifylline on PAI-1 in an Obese Population

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00770328
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arms: 2
• Duration (Months): 73
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Pentoxifylline; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of Pentoxifylline on PAI-1 in an Obese Population
• Study Start Date: May 1, 2003
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pentoxifylline Patients receive Pentoxifylline 400 mg po TID for 8 weeks.	Drug: Pentoxifylline; 400mg PO TID x 8 weeks; Other Names: Trental
Placebo Comparator: Placebo Patients take a placebo TID for 8 weeks.	Drug: Placebo; PO TID x 8 weeks; Other Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Change in PAI-1 Level [Baseline and 8 weeks]

Secondary Outcome Measures

1. Change in CRP Level [Baseline and 8 weeks]

2. Change in TNF-alpha Level [Baseline and 8 weeks]

3. Changes in the Relationship Between PAI-1, CRP, and TNF-a With Therapy. [Baseline and 8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University

Investigators

• Principal Investigator: James A S Muldowney, MD, Vanderbilt University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Muldowney, Assistant Professor, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT00770328
• Other Study ID Numbers: 030497
• First Posted: Oct 10, 2008
• Last Update Posted: Nov 30, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by James Muldowney, Assistant Professor, Vanderbilt University Medical Center: 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
• Additional relevant MeSH terms: Pentoxifylline

Study Results

Participant Flow

Arm/Group Title	Pentoxifylline	Placebo
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks	Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks
Period Title: Overall Study
STARTED	22	15
COMPLETED	9	11
NOT COMPLETED	13	4

Baseline Characteristics

Arm/Group Title	Pentoxifylline	Placebo	Total
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks	Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks	Total of all reporting groups
Overall Participants	22	15	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.7 (3.1)	38.6 (2.5)	38.2 (1.9)
Sex: Female, Male (Count of Participants)
Female	5 22.7%	5 33.3%	10 27%
Male	4 18.2%	6 40%	10 27%
Region of Enrollment (participants) [Number]
United States	22 100%	15 100%	37 100%

Outcome Measures

1. Primary Outcome

Title	Change in PAI-1 Level
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pentoxifylline	Placebo
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks	Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks
Measure Participants	9	11
Baseline	39.5 (8.3)	31.6 (7.6)
8 Weeks	28.6 (7.7)	37.9 (8.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pentoxifylline, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Change in CRP Level
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pentoxifylline	Placebo
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks	Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks
Measure Participants	9	11
Baseline	5.2 (2.5)	2.9 (0.5)
8 weeks	4.6 (1.9)	2.4 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pentoxifylline, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0114
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Change in TNF-alpha Level
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

TNF-a assay did not work properly. Meaningless data resulted including negative values which are impossible.

Arm/Group Title	Pentoxifylline	Placebo
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks	Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks
Measure Participants	0	0

4. Secondary Outcome

Title	Changes in the Relationship Between PAI-1, CRP, and TNF-a With Therapy.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Unable to complete analysis due to TNF-a assay failure (see Outcome measure #3)

Arm/Group Title	Pentoxifylline	Placebo
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks	Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks
Measure Participants	0	0

Adverse Events

Time Frame	The subjects were followed from baseline to 8 weeks.
Arm/Group Title	Pentoxifylline		Placebo
Arm/Group Description	Patients receive Pentoxifylline 400 mg po TID for 8 weeks. Pentoxifylline: 400mg PO TID x 8 weeks		Patients take a placebo TID for 8 weeks. Placebo: PO TID x 8 weeks
All Cause Mortality
	Pentoxifylline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pentoxifylline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Pentoxifylline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/22 (50%)		2/15 (13.3%)
Gastrointestinal disorders
Nausea/Vomiting	11/22 (50%)	11	0/15 (0%)	0
Bloating	0/22 (0%)	0	1/15 (6.7%)	1
Immune system disorders
Allergic Reaction	0/22 (0%)	0	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.