PrediabetesPhase 2INCITENCT01977417
Inflammation Inhibition in Prediabetic Humans
A Phase 2 study testing Salsalate in people with Prediabetes and Obese, run by Gary L. Pierce at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Prediabetes, Obese
- What is being tested?
- Salsalate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Inflammation Inhibition for Microvascular and Autonomic Dysfunction in Obese Prediabetic Humans
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.
Read the detailed description
A total of 30 healthy men and women ages 18-79 years who are obese defined as body mass index (BMI) of 30 kg/m2 or greater and with prediabetes (defined as fasting blood glucose between 100-126 mg/dl, a fasting blood glucose of 140-199 mg/dl at 120 min during an oral glucose tolerance test; or HbA1C of 6-6.5%) will be enrolled and randomized to 4-5 weeks of salsalate or placebo in the study. CONTROL GROUP: Another n=10 healthy obese men and women age 18-49 WITHOUT prediabetes will be enrolled for baseline testing but will not undergo randomization to the salsalate/placebo intervention. Therefore, total enrollment will be n=40.
All subjects will have no history of cardiovascular, metabolic or pulmonary disease as determined from medical history and physical exam, and a resting 12-lead ECG. Subjects may be on anti-hypertensive medications but will be asked to hold the medication on the morning of testing. Subjects on medications for Type I or II diabetes mellitus or for hyperlipidemia will be excluded (see complete list below). Subjects will be non-smokers or quit smoking at least one year ago. Women will have regular menses and will be tested during the early follicular phase of their menstrual cycle (within 8 days of onset of menses) to control for differences in circulating estradiol concentrations. Aim 1 will measure microvascular function and aortic wall stiffness in obese prediabetic adults before and after 1 month of salsalate or placebo. Hypothesis 1 is that chronic inflammation inhibition will improve microvascular and large elastic artery function in obese adults with prediabetes. Aim 2 will measure muscle sympathetic nervous system activity (MSNA) and baroreflex sensitivity in obese prediabetic adults before and after 1 month of salsalate or placebo. Hypothesis 2 is that chronic inflammation inhibition will decrease MSNA and improve baroreflex sensitivity in obese adults with prediabetes.
- Conditions
- Prediabetes, Obese
- Being tested
- Salsalate, Placebo
- Keywords
- Endothelial Function, Arterial Stiffness, Inflammation, Muscle Sympathetic Nervous System, Prediabetes, Autonomic function
- Medical subject headings
- Prediabetic State, Obesity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalsalateDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Salsalate | Experimental | 3.0 grams/day salsalate (1.5 g twice per day) Receives: Drug: Salsalate |
| Placebo | Placebo comparator | Placebo capsule twice per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aim 1: Vascular Endothelial Function in Obese Prediabetic Adults Before and After 1 Month of Salsalate or Placebo.
Brachial artery flow-mediated dilation
Measured: Change from baseline at 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2013 (estimated)
- Study startNov 2012
- Primary completionApr 2021
- Study completionApr 2021
Why it stopped: No funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PrediabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary L. Pierce
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gary L. Pierce, University of Iowa
- Investigators
- Gary L Pierce, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01977417
- Sponsor's protocol ID
- 201209707
- Acronym
- INCITE
- Status last verified
- Sep 2023
- First submitted
- 30 Oct 2013
- Last updated
- 11 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammation Inhibition for Microvascular and Autonomic Dysfunction in Obese Prediabetic Humans
- ClinicalTrials.gov ID
- NCT01977417
- Acronym / sponsor ID
- INCITE / 201209707
- Conditions
- Prediabetes, Obese
- Keywords
- Endothelial Function, Arterial Stiffness, Inflammation, Muscle Sympathetic Nervous System, Prediabetes, Autonomic function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No funding
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Gary L. PierceUniversity, hospital or other
- Study start
- Nov 2012 (actual)
- Primary completion
- Apr 2021 (actual)
- Study completion
- Apr 2021 (actual)
- First posted
- 6 Nov 2013 (estimated)
- Results
- Posted 11 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A total of 30 healthy men and women ages 18-79 years who are obese defined as body mass index (BMI) of 30 kg/m2 or greater and with prediabetes (defined as fasting blood glucose between 100-126 mg/dl, a fasting blood glucose of 140-199 mg/dl at 120 min during an oral glucose tolerance test; or HbA1C of 6-6.5%) will be enrolled and randomized to 4-5 weeks of salsalate or placebo in the study. CONTROL GROUP: Another n=10 healthy obese men and women age 18-49 WITHOUT prediabetes will be enrolled for baseline testing but will not undergo randomization to the salsalate/placebo intervention. Therefore, total enrollment will be n=40.
All subjects will have no history of cardiovascular, metabolic or pulmonary disease as determined from medical history and physical exam, and a resting 12-lead ECG. Subjects may be on anti-hypertensive medications but will be asked to hold the medication on the morning of testing. Subjects on medications for Type I or II diabetes mellitus or for hyperlipidemia will be excluded (see complete list below). Subjects will be non-smokers or quit smoking at least one year ago. Women will have regular menses and will be tested during the early follicular phase of their menstrual cycle (within 8 days of onset of menses) to control for differences in circulating estradiol concentrations. Aim 1 will measure microvascular function and aortic wall stiffness in obese prediabetic adults before and after 1 month of salsalate or placebo. Hypothesis 1 is that chronic inflammation inhibition will improve microvascular and large elastic artery function in obese adults with prediabetes. Aim 2 will measure muscle sympathetic nervous system activity (MSNA) and baroreflex sensitivity in obese prediabetic adults before and after 1 month of salsalate or placebo. Hypothesis 2 is that chronic inflammation inhibition will decrease MSNA and improve baroreflex sensitivity in obese adults with prediabetes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Salsalate | Experimental | Drug: Salsalate3.0 grams/day salsalate (1.5 g twice per day) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsule twice per day |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Salsalate | Drug | Salsalate |
| Placebo | Drug | Placebo |
Primary outcome
Aim 1: Vascular Endothelial Function in Obese Prediabetic Adults Before and After 1 Month of Salsalate or Placebo.
Time frame: Change from baseline at 4 weeks
Brachial artery flow-mediated dilation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary L Pierce, PhD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Salsalate in people with Prediabetes and Obese, run by Gary L. Pierce at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aim 1: Vascular Endothelial Function in Obese Prediabetic Adults Before and After 1 Month of Salsalate or Placebo. (time frame: Change from baseline at 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2023.