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Phase 2 Completed N=38 Randomized Double-blind Treatment

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

Source: ClinicalTrials.gov NCT01797575 ↗
Enrolled (actual)
38
Serious AEs
3.2%
Results posted
Apr 2018
Primary outcomePrimary: Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) — 3; 2; 5; 6 Participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS)
3; 1; 3; 4
PRIMARY
Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS)
3; 1; 3; 4
PRIMARY
Number of Patients Demonstrating a > 30% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS)
4; 3; 3; 4
PRIMARY
Number of Patients Demonstrating a > 30% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS)
4; 3; 3; 4
SECONDARY
Inflammation as Indicated by C-reactive Protein (CRP) Levels
6.85; 17.65; 5.1; 17.30; 6.82; 41.09
SECONDARY
Inflammation as Indicated by Interleukin 6 (IL-6) Levels
1.27; 3.22; .85; 2.3; .78; 3.53
SECONDARY
Inflammation as Indicated by Soluble Interleukin-2 (IL-2) Receptor Levels
SECONDARY
Inflammation as Indicated by Tumor Necrosis Factor (TNF)-Alpha Levels
SECONDARY
Oxidative Stress as Indicated by Superoxide Dismutase Activity
SECONDARY
Oxidative Stress as Indicated by Catalase Activity
SECONDARY
Oxidative Stress as Indicated by Serum Thiobarbituric Acid Reactive Substances (TBARS) Levels

Eligibility Criteria

Inclusion Criteria

  • Age 18 to 65 years
  • A diagnosis of BD type I or II according to SCID-I interview;
  • Currently in a depressive or mixed episode, based on DSM-IV/ SCID-I criteria;
  • MADRAS >20 at entry in the study;
  • No CURRENT liver, kidney, heart disease or ulcers or bleeding dyscrasia;
  • No HYSTORY of kidney dysfunction or cardiac problems;
  • ON therapeutic doses of a mood stabilizing drug (lithium, anticonvulsants, any atypical antipsychotics) or combinations for at least ONE month.
  • 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

  • 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)

  • Pregnancy
  • 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01797575). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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