Effect of Salicylate on Glucose Metabolism in Insulin Resistance States

• Sponsor: Joslin Diabetes Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00258128
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 17
• Arms: 2
• Duration (Months): 100

Study Details

Study Description

Brief Summary

Data supports diet induced obesity leads to activation of the IKK/NF-kB inflamatory pathway and that chronic inflammation leads to insulin resistance and diabetes. In rodents, salicylates inhibit IKK/NF-kB and may improve insulin sensitivity. We will study if this is true in people.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance	Drug: Salsalate; Drug: Placebo	Phase 1/Phase 2

Detailed Description

Please see the following review articles on this topic:

Shoelson SE, Lee J, Goldfine AB. (2006) Inflammation in insulin resistance. J. Clin. Invest. 116, 1793-1801.

Goldfine AB, Fonseca V and Shoelson SE (2010) Therapeutic approaches to target inflammation in type 2 diabetes. Clin Chem. 57, 162-167.

Donath MY and Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 11, 98-107.

Goldfine AB and Shoelson SE (2017) Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk. J Clin Invest. 127, 83-93.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Effect of Salicylate on Glucose Metabolism in Insulin Resistance States
• Study Start Date: Jan 1, 2000
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment This third small study has a randomized, masked, placebo controlled parallel design to compare salsalate 4.0 g/d to placebo. This is the salsalate 4.0 g/d arm.	Drug: Salsalate; Active; Other Names: Disalcid
Placebo Comparator: Placebo This third small study has a randomized, masked, placebo controlled parallel design to compare salsalate 4.0 g/d to placebo. This is the placebo arm.	Drug: Placebo; Placebo for salslate, used only in the third trial

Outcome Measures

Primary Outcome Measures

1. Glucose [4 weeks]

   fasting glucose

Secondary Outcome Measures

1. Adiponectin [4 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

age 18 to 65 years, inclusive; HbA1c >6.0% (off medication-diabetic) normal hemoglobin and hematocrit, without donation of blood in the previous 2 months; without involvement in any study evaluating an investigational drug or device for the previous 2 months; normal clotting studies; female postmenopausal or surgically sterile, or using barrier or oral contraception and with a negative pregnancy test.

Exclusion Criteria:

pregnant or lactating women; patients with persistent ketonuria or a history of ketoacidosis (suggesting the need for insulin therapy); current of previous use of insulin for glucose control; patients with abnormal liver function defined as elevation of bilirubin, alkaline phosphatase, ALT, AST, or GGTP more than 1.5 times the upper limit of normal; patients with kidney disease (serum creatinine > 1.5 mg/dL) macroalbuminuria (1+ protein on a standard urine dip-stick, or > 300 mg urinary albumin/day)- (patients with microalbuminuria will be enrolled); patients with any significant diseases or conditions, including emotional or psychiatric disorders and substance abuse, including history of binge drinking, that, in the opinion of the investigator, are likely to alter the patient's ability to complete the study; patients with metabolic acidosis (abnormal anion gap); history of gastric ulcer, dyspepsia, or upper or lower GI bleed; history of allergy to aspirin, or bleeding diathesis or currently on oral anticoagulants including warfarin, heparin, aspirin or other NSAIDs; patients with major vascular event within 6 months of screening for the study (e.g., myocardial infarction stroke, coronary artery bypass graft (CABG) surgery, angioplasty, peripheral vascular surgery); patients with chronic heart disease, or a history of myocardial infarction or stroke. Symptomatic angina pectoris or cardiac insufficiency as defined by the NYHA; classification as Functional Class III or IV; patients with HbA1C > 13% (normal range 4-6%); patients who smoke more than one pack of cigarettes daily; patients taking treatment medications known to affect insulin sensitivity (e.g. diuretics, beta-blockers); patients taking warfarin, heparin or NSAID on a chronic basis; patients with inadequately controlled serum lipid levels (total cholesterol ≥ 275 mg/dL and fasting triglycerides ≥ 450 mg/dL); patients with history of cancer within 5 years prior to screening for the study other than basal cell carcinoma; active alcohol or other substance abuse.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Joslin Diabetes Center
• National Institutes of Health (NIH)
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Steven Shoelson, Joslin Diabetes Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008 Feb;31(2):289-94. Epub 2007 Oct 24.
• Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. Review. Erratum in: J Clin Invest. 2006 Aug;116(8):2308.

• Responsible Party: Joslin Diabetes Center
• ClinicalTrials.gov Identifier: NCT00258128
• Other Study ID Numbers: CHS 00-01; R37DK051729; R01DK051729
• First Posted: Nov 24, 2005
• Last Update Posted: Apr 30, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Insulin Resistance; Salicylsalicylic acid

Study Results

Participant Flow

Recruitment Details	This study was active between 2000-2008. The location was an accademic clinic setting in the USA.
Pre-assignment Detail	Subjects were instructed to monitor fasting blood glucose levels and with symptoms of hyperglycemia or hypoglycemia, and to avoid changing dietary or exercise habits.

Arm/Group Title	Salsalate 4.0 g/d	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	8	9
COMPLETED	8	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Salsalate	Placebo	Total
Arm/Group Description	Randomized cohorts - Active	Randomized cohorts - Placebo	Total of all reporting groups
Overall Participants	8	9	17
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	9 100%	17 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (12)	54 (8)	52 (10)
Sex: Female, Male (Count of Participants)
Female	5 62.5%	4 44.4%	9 52.9%
Male	3 37.5%	5 55.6%	8 47.1%

Outcome Measures

1. Primary Outcome

Title	Glucose
Description	fasting glucose
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Receiving one dose of study drug and with measured value

Arm/Group Title	Placebo	Salsalate
Arm/Group Description	Fasting glucose	Fasting glucose
Measure Participants	9	8
Mean (Standard Deviation) [mmol/L]	7.1 (0.3)	6.4 (0.3)

2. Secondary Outcome

Title	Adiponectin
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate	Placebo
Arm/Group Description
Measure Participants	8	9
Mean (Standard Deviation) [mg/ml]	22.7 (2.5)	10.6 (2.0)

Adverse Events

Time Frame	one month
Arm/Group Title	Salsalate		Placebo
Arm/Group Description	Active Drug		Placebo - for salsalate
All Cause Mortality
	Salsalate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)
Serious Adverse Events
	Salsalate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Salsalate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)

Limitations/Caveats

Small study size, sort duration of treatment, multiple endpoints. See manuscript: Goldfine AB, et al. Clin Transl Sci. 2008 May;1(1):36-43.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.