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N-Acetyl Cysteine and Aspirin as an Adjunctive Treatment for Bipolar Disorder (SMRI-Bipolar)

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ClinicalTrials.gov Identifier: NCT01797575
Recruitment Status : Completed
First Posted : February 22, 2013
Results First Posted : April 30, 2018
Last Update Posted : April 30, 2018
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Jair Soares, The University of Texas Health Science Center, Houston

Brief Summary:

We propose to conduct a double-blind placebo-controlled trial with a widely available and prototypical non-steroidal anti-inflammatory agent, aspirin, and an antioxidant agent, NAC, involving symptomatic Bipolar Disorder type I and II patients having a depressive or mixed episode currently. This will be the first controlled study to test the hypothesis that aspirin and NAC, by themselves or in combination, will be beneficial in treating depression in bipolar disorder patients and in promoting mood stabilization.

Our study has the following Aims:

Aim I - Examine efficacy of aspirin in treating depression in bipolar patients in a double-blind placebo-controlled add-on design; Aim II - Examine efficacy of NAC in treating depression in bipolar patients in a double-blind placebo-controlled add-on design; Aim III - Examine efficacy of combined treatment with aspirin and NAC looking for synergistic, potentiating effects; Aim IV - Examine the role of markers of neuroinflammation, as possible mediators or modulators in therapeutic response in the treatment of depression in patients with Bipolar Disorder.


Condition or disease Intervention/treatment Phase
Bipolar Disorder Drug: Aspirin Dietary Supplement: N-acetyl-cysteine (NAC) Drug: Sugar Pill Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind Randomized Placebo-controlled Study of Aspirin and N-acetyl Cysteine as Adjunctive Treatments for Bipolar Disorder Patients (SMRI 11T-009)
Actual Study Start Date : January 2013
Actual Primary Completion Date : February 1, 2017
Actual Study Completion Date : February 1, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder

Arm Intervention/treatment
Active Comparator: Aspirin
research subject will be taking aspirin 1000mg (2 capsules of 500mg) every morning in addition to his/her mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations
Drug: Aspirin
aspirin 1000mg (2 capsules of 500mg) every morning in addition to his/her antidepressant and/or mood stabilizer medicine
Other Names:
  • Ecotrin
  • Bayer Aspirin
  • Bufferin
  • Acetylsalicylic Acid

Active Comparator: N-acetyl-cysteine
research subject will be taking N-acetyl-cysteine (NAC) 1000mg (2 capsules of 500mg) two times a day in addition to his/her mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations
Dietary Supplement: N-acetyl-cysteine (NAC)
taking N-acetyl-cysteine (NAC) 1000mg (2 capsules of 500mg) two times a day in addition to his/her antidepressant and/or mood stabilizer medicine
Other Names:
  • Acetylcysteine
  • N-Acetyl Cysteine
  • NAC

Active Comparator: Aspirin and NAC
research subject will be taking aspirin 1000mg (2 capsules of 500mg) every morning and NAC 1000mg (2 capsules of 500mg) two times a day in addition to his/her mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations.
Drug: Aspirin
aspirin 1000mg (2 capsules of 500mg) every morning in addition to his/her antidepressant and/or mood stabilizer medicine
Other Names:
  • Ecotrin
  • Bayer Aspirin
  • Bufferin
  • Acetylsalicylic Acid

Dietary Supplement: N-acetyl-cysteine (NAC)
taking N-acetyl-cysteine (NAC) 1000mg (2 capsules of 500mg) two times a day in addition to his/her antidepressant and/or mood stabilizer medicine
Other Names:
  • Acetylcysteine
  • N-Acetyl Cysteine
  • NAC

Placebo Comparator: Sugar Pill
research subject will be taking 4 capsules of matching sugar pill( placebo) in the morning and 2 capsules of matching placebo in the evenings in addition to his/her mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations
Drug: Sugar Pill
research subject will be taking placebo in addition to his/her antidepressant and/or mood stabilizer medicine




Primary Outcome Measures :
  1. Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Received drug for 8 weeks during week 0 to week 8 of the study ]
    The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms: 1. Apparent sadness; 2. Reported sadness; 3. Inner tension; 4. Reduced sleep; 5. Reduced appetite; 6. Concentration difficulties; 7. Lassitude; 8. Inability to feel; 9. Pessimistic thoughts; and 10. Suicidal thoughts.

  2. Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Received drug for 8 weeks during week 9 to week 16 of the study ]
    The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms: 1. Apparent sadness; 2. Reported sadness; 3. Inner tension; 4. Reduced sleep; 5. Reduced appetite; 6. Concentration difficulties; 7. Lassitude; 8. Inability to feel; 9. Pessimistic thoughts; and 10. Suicidal thoughts.

  3. Number of Patients Demonstrating a > 30% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Received drug for 8 weeks during week 0 to week 8 of the study ]
    The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms: 1. Apparent sadness; 2. Reported sadness; 3. Inner tension; 4. Reduced sleep; 5. Reduced appetite; 6. Concentration difficulties; 7. Lassitude; 8. Inability to feel; 9. Pessimistic thoughts; and 10. Suicidal thoughts. This 30% MADRS reduction was analyzed in addition to initial outcome measures of 50% MADRS reduction due to the smaller than expected study sample size.

  4. Number of Patients Demonstrating a > 30% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Received drug for 8 weeks during week 9 to week 16 of the study ]
    The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms: 1. Apparent sadness; 2. Reported sadness; 3. Inner tension; 4. Reduced sleep; 5. Reduced appetite; 6. Concentration difficulties; 7. Lassitude; 8. Inability to feel; 9. Pessimistic thoughts; and 10. Suicidal thoughts. This 30% MADRS reduction was analyzed in addition to initial outcome measures of 50% MADRS reduction due to the smaller than expected study sample size.


Secondary Outcome Measures :
  1. Inflammation as Indicated by C-reactive Protein (CRP) Levels [ Time Frame: baseline, week 8, week 16 ]
    C-reactive protein (CRP) levels are blood test markers of inflammation. Higher CRP corresponds with higher levels of inflammation. CRP is measured in milligrams per liter.

  2. Inflammation as Indicated by Interleukin 6 (IL-6) Levels [ Time Frame: baseline, week 8, week 16 ]
    Interleukin 6 (IL-6) is an interleukin that acts as a pro-inflammatory cytokine and an anti-inflammatory myokine. IL-6 is measured in picograms (pg) per milliliter (mL). Elevated interleukin-6 indicates potential immune system dysregulation and increased inflammation.

  3. Inflammation as Indicated by Soluble Interleukin-2 (IL-2) Receptor Levels [ Time Frame: baseline, week 8, week 16 ]
  4. Inflammation as Indicated by Tumor Necrosis Factor (TNF)-Alpha Levels [ Time Frame: baseline, week 8, week 16 ]
  5. Oxidative Stress as Indicated by Superoxide Dismutase Activity [ Time Frame: baseline, week 8, week 16 ]
  6. Oxidative Stress as Indicated by Catalase Activity [ Time Frame: baseline, week 8, week 16 ]
  7. Oxidative Stress as Indicated by Serum Thiobarbituric Acid Reactive Substances (TBARS) Levels [ Time Frame: baseline, week 8, week 16 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 to 65 years
  2. A diagnosis of BD type I or II according to SCID-I interview;
  3. Currently in a depressive or mixed episode, based on DSM-IV/ SCID-I criteria;
  4. MADRAS >20 at entry in the study;
  5. No CURRENT liver, kidney, heart disease or ulcers or bleeding dyscrasia;
  6. No HYSTORY of kidney dysfunction or cardiac problems;
  7. ON therapeutic doses of a mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations for at least ONE month.
  8. Allowed psychiatric co-morbid conditions, such as anxiety disorders, PTSD and substance use (as long as do NOT meet abuse or dependence criteria according to the SCID-I in the past 2 months).

Exclusion Criteria:

  1. CANNOT be on any :

    Anti-inflammatory: NSAIDs: Aspirin (bufferin, bayer aspirin, ecotrin), diflunisal (dolobid, diflunisal),Salsalate (amigesic, salflex), Ibuprofen (motrin, advil), Naproxen (naprosyn,aleve, midol extended relief), Fenoprofen (nalfon), Ketoprofen (actron), dexketoprofen(ketron D), Flurbiprofen (ansaid), Oxaprozin (daypro), Loxoprofen (loxfen, loxonin), Indomethacin (indocin, indocin SR), Sulindac (clinoril), Etodolac (lodine), Ketorolac (toradol), diclofenac (voltaren, cataflam), Nabumetone (Relafen) Piroxicam (feldene), Meloxicam (mobic), Tenoxicam (mobiflex), Lornoxicam (xefo),mefenamic acid (ponstel), meclofenamic acid (meclofenamate sodium), celecoxib (celebrex) Anticoagulants: Coumadin (Warfarin), Heparin Anti-oxidant agents Fish oil NAC ( N-acetyl cysteine)

  2. Pregnancy
  3. CANNOT change the dose of the psychotropic medications during the trial

Women Able to Become Pregnant: Participation in this study may involve risks to an embryo, fetus, or unborn child. If the subject is a female and able to become pregnant, a urine pregnancy test will be performed which must be negative prior to enrolling into the study, and the subject must agree not to become pregnant during the study. Urine pregnancy tests will be performed at Screening visit and week 8. The study staff will review adequate birth control methods with the subject and will remind her that she should not become pregnant during the study. Appropriate methods of birth control include: hormonal contraceptives (such as birth control pills, patches, and implants), barrier methods (such as a condom and diaphragms and spermicidal foam or jelly, surgical (hysterectomy or tubal ligation) or intrauterine device (IUD). The subject will be instructed to notify the study doctor immediately if there is a chance that she has become pregnant.

Also, if the subject is breast-feeding an infant or plan on breast-feeding an infant, she must notify the study doctor. It is not known if this drug is excreted in human milk; therefore, breast-feeding is not permitted during the study.

Patients can be on any mood stabilizing agents or combinations, as well as on other psychotropic medications at study entry, and the doses of those medications cannot be changed during the trial. They cannot be on any anti-inflammatory or anti-oxidant agents or anticoagulant at the point they are enrolled. If patients decompensate significantly, and/or become acutely suicidal, participation on the trial will be terminated.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01797575


Locations
United States, Texas
UT Center of Excellence on Mood Disorders
Houston, Texas, United States, 77054
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Stanley Medical Research Institute
Investigators
Principal Investigator: Jair C Soares, MD The University of Texas Health Science Center, Houston
  Study Documents (Full-Text)

Documents provided by Jair Soares, The University of Texas Health Science Center, Houston:

Additional Information:
Responsible Party: Jair Soares, Professor & Chairman - PSY-Behavioral Sciences, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01797575     History of Changes
Other Study ID Numbers: HSC-MS-12-0046
SMRI ( Other Grant/Funding Number: The Stanley Medical Research Institute )
SMRI#11T-009 ( Other Grant/Funding Number: The Stanley Medical Research Institute )
First Posted: February 22, 2013    Key Record Dates
Results First Posted: April 30, 2018
Last Update Posted: April 30, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jair Soares, The University of Texas Health Science Center, Houston:
Bipolar Disorder
Mood Disorder
Bipolar Depression
Mood Swings

Additional relevant MeSH terms:
Disease
Bipolar Disorder
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Aspirin
Acetylcysteine
N-monoacetylcystine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Protective Agents