Salsalate as an Adjunctive Treatment for Patients With Schizophrenia

• Sponsor: University of Massachusetts, Worcester (Other)
• Overall Status: Completed
• CT.gov ID: NCT01578486
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 49
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a 12-week, open-label trial of salsalate 3 g/day as an adjunctive treatment in 15 schizophrenia subjects to examine salsalate's effect on psychopathology, cognitive functioning, and metabolic parameters.

Potential subjects will be identified by their clinicians at the Freedom Trail Clinic, or Massachusetts General Hospital. A total of 15 subjects will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: salsalate	Phase 4

Detailed Description

The specific aims include:

Primary aims:

1. Examine the efficacy of salsalate (3g/day) in improving positive and negative symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS).

2. Examine the efficacy of salsalate in improving cognition as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) composite score.

Secondary aims:

1. Examine salsalate's effects on inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), TNF-α and IL-6.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Salsalate as an Adjunctive Treatment for Patients With Schizophrenia
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: salsalate open-label trial of salsalate 3g/day	Drug: salsalate; open-label trial of salsalate 3g/day for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. PANSS Total Score [Baseline and 12 weeks]

   Positive and negative symptoms of schizophrenia will be measured by total score on all subscales of the Positive and Negative Syndrome Scale (PANSS; score range 30-210). Higher scores correspond with worse outcomes.

2. SANS Total Score [Baseline, 12 weeks]

   Negative symptoms of schizophrenia will be measured by total score on the Scale for Assessment of Negative Symptoms (SANS; score range 0-100). Higher scores correspond with worse outcomes.

3. MATRICS Composite Score [Baseline, 12 weeks]

   Improved cognition will be measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) assessment. The MATRICS assessment includes a battery of tests, and the composite t-score measures cognition across 7 domains including speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. A higher score indicates better cognition.

4. PANSS Positive Score [Baseline, 12 weeks]

   Subscale of Positive and Negative Syndrome Scale that specifically measures positive symptoms. The scores range from 7-49, with higher scores representing a worse outcome.

5. PANSS- Negative Score [Baseline, 12 weeks]

   Subscale of Positive and Negative Syndrome Scale that specifically measures negative symptoms. The scores range from 7-49, with higher scores representing a worse outcome.

Secondary Outcome Measures

1. Hs-CRP [Baseline, 12 weeks]

   High-sensitivity C-reactive protein (hs-CRP) will be measured in mg/L in order to detect inflammation. Higher hs-CRP values correspond to higher levels of inflammation.

2. TNF-alpha [Baseline,12 weeks]

   Tumor necrosis-alpha factor will be measured to assess inflammation levels.

3. IL-6 [Baseline, week 12]

   IL-6 (interleukin 6) is a marker used to measure inflammation.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 18-65 years;

• Diagnosis of schizophrenia or schizoaffective disorder;

• Stable dose of the current antipsychotic drug for at least one month;

• Well established compliance with outpatient treatment per treating clinician's judgment;

• Able to complete the cognitive assessment battery (must be English speaking);

• Female subjects will be eligible to participate in the study if they are of non-childbearing potential or of child-bearing potential and willing to practice appropriate birth control methods during the study.

Exclusion Criteria:

• Inability to provide informed consent;

• Current substance abuse;

• Psychiatrically unstable per treating clinician's judgment;

• Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases;

• Currently on immunosuppressant medication including oral steroids;

• Use of anti-coagulants (heparin, LMWH, warfarin, cilostazol, clopidogrel, dabigatran);

• History of chronic infection (including, HIV and hepatitis), malignancy, organ transplantation, blood dyscrasia, central nervous system demyelinating disorder, and any other known autoimmune or inflammatory condition;

• Experienced asthma, urticaria or allergic type reaction after taking aspirin, salsalate, or other NSAIDS;

• Pregnancy or breastfeeding;

• Pre-existing chronic tinnitus.

• Known hypersensitivity to salsalate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Massaschusetts Medical School	Worcester	Massachusetts	United States	01605

Sponsors and Collaborators

• University of Massachusetts, Worcester
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Xiaoduo Fan, MD, MPH, MS, UMass Medical School
• Study Director: Matthew R Goodnow, BS, UMass Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Xiaoduo Fan, Principal Investigator, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT01578486
• Other Study ID Numbers: 2011-P-000798
• First Posted: Apr 17, 2012
• Last Update Posted: May 8, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Xiaoduo Fan, Principal Investigator, University of Massachusetts, Worcester: Schizophrenia; Cognition; Metabolism; Antipsychotics; Psychopathology
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Salicylsalicylic acid

Study Results

Participant Flow

Pre-assignment Detail	A total of 17 subjects consented and were screened, 4 of which were screen fails. The remaining 13 received the study medication.

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Period Title: Overall Study
STARTED	13
COMPLETED	8
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.8 (9.8)
Sex: Female, Male (Count of Participants)
Female	2 25%
Male	6 75%

Outcome Measures

1. Primary Outcome

Title	PANSS Total Score
Description	Positive and negative symptoms of schizophrenia will be measured by total score on all subscales of the Positive and Negative Syndrome Scale (PANSS; score range 30-210). Higher scores correspond with worse outcomes.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	58.2 (11.4)
Week 12	53.5 (11.9)

2. Primary Outcome

Title	SANS Total Score
Description	Negative symptoms of schizophrenia will be measured by total score on the Scale for Assessment of Negative Symptoms (SANS; score range 0-100). Higher scores correspond with worse outcomes.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	33.0 (15.7)
Week 12	33.0 (12.9)

3. Primary Outcome

Title	MATRICS Composite Score
Description	Improved cognition will be measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) assessment. The MATRICS assessment includes a battery of tests, and the composite t-score measures cognition across 7 domains including speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. A higher score indicates better cognition.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	27.9 (11.9)
Week 12	31.6 (15.2)

4. Primary Outcome

Title	PANSS Positive Score
Description	Subscale of Positive and Negative Syndrome Scale that specifically measures positive symptoms. The scores range from 7-49, with higher scores representing a worse outcome.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	13.0 (5.4)
Week 12	10.9 (4.4)

5. Primary Outcome

Title	PANSS- Negative Score
Description	Subscale of Positive and Negative Syndrome Scale that specifically measures negative symptoms. The scores range from 7-49, with higher scores representing a worse outcome.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	18.5 (6.5)
Week 12	17.4 (6.1)

6. Secondary Outcome

Title	Hs-CRP
Description	High-sensitivity C-reactive protein (hs-CRP) will be measured in mg/L in order to detect inflammation. Higher hs-CRP values correspond to higher levels of inflammation.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	3.0 (1.2)
Week 12	2.0 (1.2)

7. Secondary Outcome

Title	TNF-alpha
Description	Tumor necrosis-alpha factor will be measured to assess inflammation levels.
Time Frame	Baseline,12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	8.2 (3.7)
Week 12	8.7 (3.6)

8. Secondary Outcome

Title	IL-6
Description	IL-6 (interleukin 6) is a marker used to measure inflammation.
Time Frame	Baseline, week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
Measure Participants	8
Baseline	2.2 (0.87)
Week 12	2.3 (1.00)

Adverse Events

Arm/Group Title	Salsalate
Arm/Group Description	salsalate: open-label trial of salsalate 3g/day for 12 weeks.
All Cause Mortality
	Salsalate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Salsalate
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Salsalate
	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)
Gastrointestinal disorders
Stomach/Abdominal discomfort	1/8 (12.5%)	1
General disorders
Nausea/Vomiting	1/8 (12.5%)	1
Lightheadedness	1/8 (12.5%)	1
Headache	2/8 (25%)	2
Weakness	1/8 (12.5%)	1
Bloody urine	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.