Beneficial Effect of Salicylates: Insulin Action, Secretion or Clearance?

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02007577
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The possibility that obesity-associated inflammatory changes may play a role in the pathogenesis of type 2 diabetes (2DM) has led to increased interest in the possibility that salicylates might represent a useful treatment to improve glucose tolerance. Several studies, performed in patients with 2DM, as well as in nondiabetic, obese individuals, have demonstrated that salicylates have beneficial effects on glucose and insulin metabolism, but have not led to a coherent view as to the mechanism(s) involved.

In this research proposal we will use specific methods to quantify insulin mediated glucose uptake (IMGU), glucose-stimulated insulin secretion rate (GS-ISR), and insulin clearance (I-Cl) in overweight/obese, nondiabetic, insulin resistant individuals. We will use the insulin suppression test (IST) to quantify IMGU in nondiabetic, overweight/obese volunteers to identify those individuals who are sufficiently insulin resistant to be enrolled in this study. We will then use the graded glucose infusion technique in these insulin resistant subjects to generate specific measures of both GS-IS and I-Cl. Following these baseline measurements, salsalate or placebo will be administered for one month to the participants, after which time the IST and the graded glucose infusion will be repeated to quantify and compare the changes in IMGU, GS-ISR, and I-Cl that have resulted from salsalate versus placebo. These results will provide for the first time quantitative data of the effect of salicylates on IMGU, GS-ISR, and I-Cl in overweight/obese, insulin resistant, nondiabetic individuals.

Condition or Disease	Intervention/Treatment	Phase
Pre Diabetes; Insulin Resistant	Drug: salsalate; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Official Title: Beneficial Effect of Salicylates: Insulin Action, Secretion or Clearance?
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: salsalate 3500mg in 2 divided doses a day Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner	Drug: salsalate; Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner
Placebo Comparator: placebo Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner	Drug: Placebo; Participants will take 3 tablets with breakfast and 4 tablets with dinner

Outcome Measures

Primary Outcome Measures

1. Quantification of Insulin Action With the Insulin Suppression Test (IST) [after treatment for one month]

   Compare changes in insulin sensitivity as assesses by the IST before and after treatment between salsalate and placebo group

Secondary Outcome Measures

1. Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT) [one month on treatment]

   compare changes in insulin clearance as assessed by the GGIT before and after treatment with salsalate to placebo

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy volunteers,

• BMI 25-35kg/m2,

• Without severe anemia, kidney, liver disease or any current GI ulcers or bleeding

• Or on any medication contraindicated with salsalate

Exclusion Criteria:

• Recent history of GI bleed or ulcers,

• CVD or on anticoagulants

• Severe kidney or liver disease

• Allergies to aspirin

• Taking aspirin or anti inflammatory medication on a regular basis and cannot be taken off for the duration of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Gerald M Reaven, M.D., Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gerald M Reaven, Professor Emeritus, Stanford University
• ClinicalTrials.gov Identifier: NCT02007577
• Other Study ID Numbers: 19254
• First Posted: Dec 11, 2013
• Last Update Posted: May 5, 2016
• Last Verified: Apr 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Gerald M Reaven, Professor Emeritus, Stanford University: insulin resistant
• Additional relevant MeSH terms: Prediabetic State; Salicylsalicylic acid

Study Results

Participant Flow

Arm/Group Title	Salsalate 3500mg in 2 Divided Doses a Day	Placebo
Arm/Group Description	Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner salsalate: Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner	Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner Placebo: Participants will take 3 tablets with breakfast and 4 tablets with dinner
Period Title: Overall Study
STARTED	27	14
COMPLETED	26	13
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Salsalate 3500mg in 2 Divided Doses a Day	Placebo	Total
Arm/Group Description	Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner salsalate: Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner	Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner Placebo: Participants will take 3 tablets with breakfast and 4 tablets with dinner	Total of all reporting groups
Overall Participants	26	13	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (10)	54 (10)	54 (10)
Sex: Female, Male (Count of Participants)
Female	12 46.2%	4 30.8%	16 41%
Male	14 53.8%	9 69.2%	23 59%

Outcome Measures

1. Primary Outcome

Title	Quantification of Insulin Action With the Insulin Suppression Test (IST)
Description	Compare changes in insulin sensitivity as assesses by the IST before and after treatment between salsalate and placebo group
Time Frame	after treatment for one month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate 3500mg in 2 Divided Doses a Day	Placebo
Arm/Group Description	Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner salsalate: Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner	Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner Placebo: Participants will take 3 tablets with breakfast and 4 tablets with dinner
Measure Participants	26	13
Median (95% Confidence Interval) [mmol/L]	-3	2

2. Secondary Outcome

Title	Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT)
Description	compare changes in insulin clearance as assessed by the GGIT before and after treatment with salsalate to placebo
Time Frame	one month on treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate 3500mg in 2 Divided Doses a Day	Placebo
Arm/Group Description	Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner salsalate: Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner	Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner Placebo: Participants will take 3 tablets with breakfast and 4 tablets with dinner
Measure Participants	26	13
Median (95% Confidence Interval) [pmol/min x 4h]	-6	0

Adverse Events

Arm/Group Title	Salsalate 3500mg in 2 Divided Doses a Day		Placebo
Arm/Group Description	Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner salsalate: Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner		Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner Placebo: Participants will take 3 tablets with breakfast and 4 tablets with dinner
All Cause Mortality
	Salsalate 3500mg in 2 Divided Doses a Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Salsalate 3500mg in 2 Divided Doses a Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Salsalate 3500mg in 2 Divided Doses a Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/27 (3.7%)		0/14 (0%)
Ear and labyrinth disorders
tinnitus	1/27 (3.7%)	4	0/14 (0%)	0
Gastrointestinal disorders
3 years	1/27 (3.7%)	1	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

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.