Inflammation Inhibition in Prediabetic Humans (INCITE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Iowa
Sponsor:
Information provided by (Responsible Party):
University of Iowa
ClinicalTrials.gov Identifier:
NCT01977417
First received: October 30, 2013
Last updated: November 5, 2013
Last verified: October 2013
  Purpose

Prediabetes, characterized by elevated fasting blood sugar or exaggerated blood sugar response to sugar ingestion, effects over 79 million adult Americans and is a precursor to the development of Type 2 diabetes. Importantly, approximately 42% of Iowans (950,000) have diabetes and 32% (670,000) have prediabetes with the majority of those with prediabetes going undiagnosed. Adults with prediabetes demonstrate early signs of cardiovascular and nervous system abnormalities and are at high risk for developing overt diabetes unless aggressive lifestyle (weight loss, exercise) or pharmacological interventions are employed. Interestingly, data in recent years has linked obesity and diabetes to chronic inflammation of the blood vessels and brain areas that regulate blood pressure. Therefore, the current study will test whether a commonly used aspirin-like anti-inflammatory drug called salsalate, will improve blood vessel health and nervous system dysfunction in adults with prediabetes. Eligible subjects will have measurements of blood pressure, blood vessel function in the arms and eyes, assessments of nerve activity, and blood samples taken before and after 4 weeks of ingesting an FDA approved aspirin-like drug called salsalate. The study is important because it will identify a potentially new pharmacological strategy to treat vascular and nervous system abnormalities in overweight and obese adults with early stage type 2 diabetes using an inexpensive, generically available drug with an excellent safety record that has been used for decades to treat chronic inflammatory conditions such as rheumatoid arthritis. If proven effective, this will provide preliminary support for the concept of targeting inflammation as a new clinical approach to treating early diabetes related complications. Furthermore, the current pilot study will provide support for developing a larger clinical trial using salsalate that could potentially then be extended to patients with type 2 diabetes and cardiovascular disease, as well as lead to the development of new anti-inflammatory agents with greater specificity for selective inflammatory pathways.


Condition Intervention Phase
Prediabetes
Obese
Drug: Salsalate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Inflammation Inhibition for Microvascular and Autonomic Dysfunction in Obese Prediabetic Humans

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Aim 1: To measure microvascular endothelial function and aortic wall stiffness in obese prediabetic adults before and after 1 month of salsalate or placebo. [ Time Frame: Change from baseline at 4 weeks ] [ Designated as safety issue: No ]
    Forearm blood flow responses to incremental intra-brachial artery infusions of acetylcholine and sodium nitroprusside; carotid-femoral pulse wave velocity


Secondary Outcome Measures:
  • Aim 2: To measure sympathetic nervous system activity and baroreflex sensitivity in obese prediabetic adults before and after 1 month of salsalate or placebo. [ Time Frame: Change from baseline at 4 weeks ] [ Designated as safety issue: No ]
    Muscle sympathetic nervous system activity (MSNA) via peroneal nerve microneurography; Baroreflex sensitivity via sequence technique


Estimated Enrollment: 40
Study Start Date: November 2012
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Salsalate
3.0 grams/day salsalate (1.5 g twice per day)
Drug: Salsalate
Placebo Comparator: Placebo
Placebo capsule twice per day
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.

    • Age is > or = 18 and < or = 49 years (older)
    • Obese defined as body mass index > or = 30 kg/m2
    • Prediabetic defined as fasting blood glucose 100-126 mg/dl, blood glucose between 140-199 mg/dl at 120 min of oral glucose tolerance test
    • healthy, as determined by health history questionnaire, medical history and physical examination by physician or nurse practitioner, blood chemistries, resting blood pressure and exercise 12-lead ECG
    • blood chemistries indicative of normal renal function (creatinine <2.2 mg/dl), liver (<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L)
    • If currently receiving treatment with or taking any of the following supplements, be willing and able to discontinue taking them for 2 weeks prior and throughout the treatment period: Vitamin C, E or other multivitamins containing vitamin C or E; nutraceuticals containing vitamin C or E
    • No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), Type 1 or 2 diabetes mellitus, or peripheral arterial disease
    • Sedentary or recreationally active defined as performs regular aerobic exercise (30 min or more of vigorous walking, jogging, swimming, cycling, etc) less than 2 days/week or less than 12 days/month over the last year
    • Non-smokers, defined as no history of smoking, no smoking for at least the past 1 year
    • Normal resting 12-lead ECG.

Exclusion Criteria:

  • History of cardiovascular disease such as myocardial infarction, stroke, heart failure with or without LV ejection fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, Type 2 diabetes and Type 1 diabetes

    • Smoking or history of smoking within past one year
    • History of gastric ulcers, bleeding disorders, dyspepsia, severe gastroesophageal reflux disease (GERD), or metabolic acidosis
    • History of asthma or lung disease (chronic obstructive pulomonary disease, COPD)
    • Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)
    • Serious neurologic disorders including seizures
    • History of renal failure, dialysis or kidney transplant
    • Serum creatinine > 2.2 mg/dL, or hepatic enzyme concentrations > 3 times the upper limit of normal
    • History of HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening.
    • Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
    • History of recent chicken pox, shingles or influenza (ie., risk of Reye's syndrome) Recent flu-like symptoms within the past 2 weeks
    • Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
    • Women with history of hormone replacement therapy within the past 6 months
    • History of rheumatoid arthritis, Grave's disease, systemic lupus erythamatosis, and Wegener's granulomatosis;
    • Taking medications for diabetes mellitus, kidney disease, liver disease, asthma, sepsis or seizure disorders;
    • Taking lipid lowering (e.g., statins, niacin), glycemic control (e.g. metformin, insulin), anticoagulation, anti-seizure, anti-depression or antipsychotic agents
    • History of co-morbid condition that would limit life expectancy to < 6 months.
    • It is unknown if Salsalate is transferred in seminal fluid of men. However, it is recommended that proper protection such as a condom be used during intercourse during the study.
    • Concomitant treatment with: aspirin, baby aspirin, indomethacin, naproxen (Aleve), acetaminophen (Tylenol), ibuprofen (Advil, Motrin), any other non-steroidal anti-inflammatory drugs; cox-2 inhibitors (Celebrex, Vioxx, etc); allopurinol (Zyloprim, Lopurin, Alopurin; coumadin (Wafarin), enoxaparin (Lovenox); clopidogrel (Plavix); dypyridamole (Persantine); heparin; diabetic medications (Metformin, glyburide, insulin, etc), TZDs (Avandia, Rezulin, Actos); corticosteroids (prednisone); methotrexate, infliximib (Remicade), etaneracept (Enbrel); levothyroxine (Levoxyl, Synthroid, Levoxyl, Unithroid); Levodopa; Phosphodiesterase (PDE) 5 inhibitors (e.g., Viagra®, Cialis®, Levitra®, or Revatio®); PDE 3 inhibitors (e.g., cilostazol, milrinone, or vesnarinone); lithium
    • May participate if use of the following medications are discontinued 2 weeks prior to participation: salicylate medications, aspirin, antioxidants, herbal supplements, vitamins, omega-3 fatty acids; cox-2 inhibitors (Celebrex, Vioxx, etc)
    • May participate if no use of the following medications in the 48 hours prior to experimental visits: naproxen (Aleve), acetaminophen (Tylenol), ibuprofen (Advil, Motrin), other any non-steroidal anti-inflammatory drugs
    • Vulnerable populations (prisoners, etc.) are not included in this study because we are studying healthy middle-aged/older adults.
    • Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
    • Hemoglobin <12 mg/dl for men; < 10 mg/dl for women
    • History of alcohol abuse or >10 alcoholic units per week (1 unit= 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 oz alcohol)
    • Low platelets (<100,000 cu mm)
    • On weight loss drugs (e.g., Xenical (orilistat), Meridia (sibutramine), Acutrim (phenylpropanol-amine), or similar over-the-counter medications) within 3 months of screening
    • Any surgery within 30 days of screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01977417

Contacts
Contact: Veronica Howsare veronica-howsare@uiowa.edu

Locations
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52240
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: Gary L Pierce, PhD University of Iowa
  More Information

No publications provided

Responsible Party: University of Iowa
ClinicalTrials.gov Identifier: NCT01977417     History of Changes
Other Study ID Numbers: 201209707
Study First Received: October 30, 2013
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Iowa:
Endothelial Function
Arterial Stiffness
Inflammation
Muscle Sympathetic Nervous System
Prediabetes
Autonomic function

Additional relevant MeSH terms:
Prediabetic State
Inflammation
Glucose Intolerance
Pathologic Processes
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Sodium Salicylate
Salicylsalicylic acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014