Inflammation Inhibition in Prediabetic Humans

NCT01977417 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201209707
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prediabetes; Obese

Keywords

Endothelial Function; Arterial Stiffness; Inflammation; Muscle Sympathetic Nervous System; Prediabetes; Autonomic function

Outcome Measures

Primary Outcomes (1)

• Aim 1: Vascular Endothelial Function in Obese Prediabetic Adults Before and After 1 Month of Salsalate or Placebo.

  Brachial artery flow-mediated dilation

  Change from baseline at 4 weeks

Study Arms (2)

Salsalate

EXPERIMENTAL

3.0 grams/day salsalate (1.5 g twice per day)

Drug: Salsalate

Placebo

PLACEBO COMPARATOR

Placebo capsule twice per day

Drug: Placebo

Interventions

Salsalate DRUG

Salsalate

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Gary L. Pierce: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52240, United States

Location

MeSH Terms

Conditions

Prediabetic State; Obesity; Inflammation

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Results Point of Contact

• Title: Gary Pierce, PhD
• Organization: University of Iowa

gary-pierce@uiowa.edu

319-335-9487

Study Officials

• Gary L Pierce, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 6, 2013
• Study Start: November 1, 2012
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: September 11, 2023
• Results First Posted: September 11, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)