Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00837590

Enrollment

Registered

2009-02-05

Start date

2009-03-31

Completion date

2010-08-31

Last updated

2019-08-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Pre-diabetes

Keywords

Vascular function, Glucose tolerance, Obesity, Pre-diabetes

Brief summary

Aims: 1. Does inflammation contribute importantly to concurrent defects in vascular and metabolic dysfunction in human pre-diabetic obesity? 2. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin? 3. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with lisinopril?

Detailed description

We set out to pursue the following Aims: 1. Does inflammation contribute importantly to concurrent defects in vascular and metabolic dysfunction in human pre-diabetic obesity? Pilot studies were performed exploring the acute actions of salsalate on vascular function, the chronic actions of salasate in obese individuals, and actions of chronic salsalate to prevent vascular dysfunction induced by fatty acids in lean individuals. 2. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin? No studies were performed 3. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with lisinopril? No studies were performed The intent of the current project is to efficiently and at low cost generate preliminary data along each of these lines of questioning, studying the minimum number of subjects required to assess the viability of the question using the current measurement approaches.

Interventions

DRUGChronic salsalate

Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.

DRUGAcute Salsalate

Subjects will receive a single oral dose of 2 gram of oral salsalate

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* healthy * normotensive (BP\<140/95 mmHg) * lean and obese * 18 and 55 years * women must be premenopausal

Exclusion criteria

* use of pharmacologic agents or recreational drugs, with the exception of occasional use of non-narcotic pain medications * blood pressure (\>140/90 mmHg) * elevated cholesterol (LDL \>130 mg/dL) * diabetes mellitus (by ADA criteria) * evidence of coronary and/or peripheral vascular disease by history and physical exam * \>5 kg change in weight in the preceding 3 months * chronic systemic illness with recognized metabolic effects * hepatitis C and HIV * recognized systemic inflammatory or autoimmune processes such as rheumatoid arthritis or systemic lupus erythematosis * Raynaud's phenomenon or other abnormalities of hand or finger perfusion * regular participation in endurance or high-performance athletic activity * history of aspirin or salsalate sensitivity including aspirin-induced asthma * prior treatment with salsalate, pentoxyfilline, or monoclonal anti-TNFalpha antibodies * pregnancy * liver transaminase levels \>3 times the upper limit of normal * creatinine \>1.5 mg/dL * history of a cellular immunodeficiency-related opportunistic infections, such as an endemic mycosis (eg. histoplasmosis) or mycobacterial infection (eg tuberculosis) * reactive tuberculin skin test * history of malignancy except for basal cell carcinoma of the skin

Design outcomes

Primary

Measure	Time frame	Description
Vascular Function	Measured at baseline and after a single oral dose of salsalate (Acute) or 2 months' treatment with salsalate (Chronic)	The primary endpoints of interest is flow-mediated vasodilation

Countries

United States

Participant flow

Recruitment details

All subjects were self-referred to the clinic for this study.

Pre-assignment details

Subjects were excluded primarily for anemia based on screening labs or failure to return for clinic visits.

Participants by arm

Arm	Count
Acute Salsalate Nondiabetic lean and obese subjects will be studied in this arm. Subjects will be studied at baseline and after a single dose of salsalate. salsalate : Subjects will receive a single day of 4 gram/day of oral salsalate divided into 3 doses.	6
Chronic Salsalate - Lean Nondiabetic lean subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months of treatment with salsalate. Salsalate : Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.	5
Chronic Salsalate - Obese Nondiabetic obese subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months of treatment with salsalate. Salsalate : Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.	5
Total	16

Baseline characteristics

Characteristic	Acute Salsalate	Chronic Salsalate - Lean	Chronic Salsalate - Obese	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	6 Participants	5 Participants	5 Participants	16 Participants
Region of Enrollment United States	6 participants	5 participants	5 participants	16 participants
Sex: Female, Male Female	2 Participants	2 Participants	2 Participants	6 Participants
Sex: Female, Male Male	4 Participants	3 Participants	3 Participants	10 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 5	0 / 5
other Total, other adverse events	0 / 6	0 / 5	0 / 5
serious Total, serious adverse events	0 / 6	0 / 5	0 / 5

Outcome results

Primary