Free Fatty Acids-Induced Hypertension in Obese Subjects (Aim #2)

NCT02406586 | Completed Results DMC

• 1 other identifier: IRB00009277a
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if salsalate, an Nuclear factor-kappaB (NF-κB) mediated inflammation inhibitor, or carvedilol, an α- and β-blocker, will protect against free fatty acid induced hypertension, insulin resistance, endothelial dysfunction, inflammation and oxidative stress, and autonomic dysfunction in obese normotensive subjects.

Conditions

Hypertension; Diabetes

Outcome Measures

Primary Outcomes (16)

• Change in Systolic Blood Pressure.

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 4 hours during Intralipid infusion.

  Pre-dose (Baseline), within 4 hours at Baseline visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. from Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 8 hours during Intralipid.

  Pre-dose (Baseline), within 8 hours at Baseline visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

  Pre-dose (Baseline), within 12 hours at Baseline visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 16 hours during Intralipid infusion.

  Pre-dose (Baseline), within 16 hours at Baseline visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 20 hours during Intralipid infusion.

  Pre-dose (Baseline), within 20 hours at Baseline visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion.

  Pre-dose (Baseline), within 24 hours at Baseline visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 4 hours during Intralipid infusion.

  Pre-dose (Week 6), within 4 hours at Week 6 visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure from at Week 6 from pre-dosing with Intralipid to 8 hours during Intralipid infusion.

  Pre-dose (Week 6), within 8 hours at Week 6 visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

  Pre-dose (Week 6), within 12 hours at Week 6 visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 16 hours during Intralipid infusion.

  Pre-dose (Week 6), within 16 hours at Week 6 visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 20 hours during Intralipid infusion.

  Pre-dose (Week 6), within 20 hours at Week 6 visit

• Change in Systolic Blood Pressure

  Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 24 hours during Intralipid infusion.

  Pre-dose (Week 6), within 24 hours at Week 6 visit

• Change in Flow-mediated Dilation

  The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

  Pre-dose (Baseline), within 12 hours at Baseline visit

• Change in Flow-mediated Dilation

  The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion

  Pre-dose (Baseline), within 24 hours at Baseline visit

• Change in Flow-mediated Dilation

  The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

  Pre-dose (Week 6), within 12 hours at Week 6 visit

• Change in Flow-mediated Dilation

  The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion

  Pre-dose (Week 6), within 24 hours at Week 6 visit

Secondary Outcomes (7)

• Change in Diastolic Blood Pressure From Baseline to 6 Weeks

  Baseline, 6 weeks

• Change in Oxidative Stress Markers.

  Baseline, 6 weeks

• Change in Augmentation Index (AIx)

  Baseline, 6 weeks

• Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6)

  Baseline, 6 weeks

• Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks

  Baseline, 6 weeks

Study Arms (3)

Salsalate

EXPERIMENTAL

Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.

Drug: Salsalate; Drug: Intralipid 20%

Carvedilol

EXPERIMENTAL

Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.

Drug: Carvedilol; Drug: Intralipid 20%

Placebo

PLACEBO COMPARATOR

Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose will be increased to two placebo tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.

Drug: Placebo; Drug: Intralipid 20%

Interventions

Salsalate DRUG

Salsalate 750 mg

Also known as: Disalcid, NSAID

Salsalate

Carvedilol DRUG

Carvedilol 3.125 mg

Also known as: Coreg

Carvedilol

Placebo DRUG

One tablet

Placebo

Intralipid 20% DRUG

24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)

Also known as: 20% I.V. Fat Emulsion

Carvedilol; Placebo; Salsalate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females
• Obese subjects (body mass index (BMI) ≥ 30 kg/m\^2)
• and 65 years
• Blood pressure reading \< 140/80 mm Hg and no prior history of hypertension

You may not qualify if:

• History of diabetes mellitus
• History of hypertension
• Fasting triglyceride levels \> 250 mg/dL
• Liver disease (ALT 2.5x \> upper limit of normal)
• Serum creatinine ≥1.5 mg/dL
• Smokers, drug or alcohol abuse
• Mental condition rendering the subject unable to understand the scope and possible consequences of the study
• Female subjects who are pregnant or breast feeding

Sponsors & Collaborators

• Emory University: lead
• American Diabetes Association: collaborator

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

MeSH Terms

Conditions

Hypertension; Diabetes Mellitus

Interventions

salicylsalicylic acid; Anti-Inflammatory Agents, Non-Steroidal; Carvedilol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Guillermo Umpierrez
• Organization: Emory University

geumpie@emory.edu

404-778-1665

Study Officials

• Guillermo Umpierrez, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 2, 2015
• Study Start: July 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: January 8, 2019
• Results First Posted: May 28, 2015

Record last verified: 2018-12

Locations

US (1)