N-Acetyl Cysteine Supplementation in Therapy Refractory Major Depressive Disorders

NCT02972398 | Unknown DMC

• 1 other identifier: NAC-2015-TJAH
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the efficacy of N-acetylcysteine (NAC) add-on to antidepressant medication in treating patients who do not relieve during standard antidepressant treatment for 6 weeks at least. Meanwhile, secondary outcomes will include changes in some biomarkers and on specifically local brain activity (functional Magnetic Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). The hypothesis of this study is that NAC has positive effects on refractory major depressive disorder patients with increased inflammatory activity.

Conditions

Major Depressive Disorders

Keywords

treatment resistant depression; N-Acetyl Cysteine; inflammation mediators; oxidative stress; brain imaging

Outcome Measures

Primary Outcomes (1)

• The change from baseline Hamilton Depression Rating Scale (HAMD)-17 items at week2,4,6,8,10,and 12.

  The main objective is to investigate whether daily oral NAC administration in addition to regular treatment with an antidepressant will alleviate the severity of MDD symptoms as measured with the HAMD-17 after 12 weeks of treatment compared to placebo addition, and we also look at other time points, such as week 2,4,6,8,and 10.

  baseline, Week 2,4,6,8,10, and 12

Secondary Outcomes (8)

• The change from baseline HAMD-17 items at week14,16,18,and 20.

  baseline, Week 14,16,18,and 20.

• The effects of augmentation treatment with NAC on scores in Beck Anxiety Inventory (BAI)

  baseline, Week 4,8,12,16,and 20.

• The effects of augmentation treatment with NAC on scores in Inventory of Depressive Symptoms-Self-Rated (IDS-SR)

  baseline, Week 4,8,12,16,and 20.

• The effects of augmentation treatment with NAC on scores in WHO Disability Assessment Schedule Ⅱ (WHODAS-Ⅱ)

  baseline, Week 4,8,12,16,and 20.

• The effects of augmentation treatment with NAC on scores in Montreal Cognitive Assessment (MoCA)

  baseline, Week 4,8,12,16,and 20.

Study Arms (2)

NAC group

EXPERIMENTAL

Participants of "NAC group" receive 1000 mg NAC twice daily for 12 weeks as add-on to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenalin reuptake inhibitor (SNRI)

Drug: N-acetylcysteine

Placebo group

PLACEBO COMPARATOR

Participants of "Placebo group" receive placebo matched with NAC twice daily for 12 weeks as add-on to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenalin reuptake inhibitor (SNRI)

Drug: placebo comparator of N-acetylcysteine

Interventions

N-acetylcysteine DRUG

Participants of interventional group receive 1000mg N-acetylcysteine twice daily for 12 weeks.

Also known as: YiWeiShi

NAC group

placebo comparator of N-acetylcysteine DRUG

Participants of placebo group receive placebo comparator matching with N-acetylcysteine twice daily for 12 weeks.

Placebo group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a current episode of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) diagnosed with SCID
• an age between 18 and 65 years
• a total score of HAMD-17 ≥ 17
• a CRP level between 0.85 and 10 mg/L (The CRP range is based on literature values for mild to moderate chronic inflammation, while values \> 10 mg/L point at acute inflammation. A pilot study at the Tianjin Hospital (n=62) indicated that approximately one third of all patients with MDD will have CRP values within this range). insufficient response to 1 or more antidepressants given for at least 6 weeks and in an adequate dose during the current episode
• stable dose of the current antidepressant drug for at least 2 weeks prior to initiation of the study
• Patients are allowed to use benzodiazepines (BZD) to relieve anxiety during the first phase of antidepressant treatment (Anding Hospital protocol). Benzodiazepines may also be prescribed because of sleeping problems during the trial. BZD use will be recorded at all assessments during the trial and after follow-up.
• Patients are compliant with treatment according to the judgement of the treating clinician.
• 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. Clinical patients always get a pregnancy test before start of treatment.
• Participant or guardian has to sign informed consent. The patients' guardians will sign the informed consent on behalf of the participants when the capacity of participants to consent is compromised.

You may not qualify if:

• A history of manic episode
• Use of mood stabilizer
• Use of antipsychotic medication with more than half of the maximum dosage suggested in the instruction
• History of substance abuse or dependence
• An allergic reaction to NAC or any component of the preparation
• Severe somatic diseases that might interfere with regular antidepressant treatment including conditions such as kidney and liver failure, uncontrolled hypertension, cardiovascular, cerebrovascular and pulmonary disease, thyroid disease, diabetes, epilepsy and asthma.
• Use of anti-inflammatory medication for longer than 7 days in the last two months preceding the trial
• Use of immunosuppressive medication such as oral steroid hormones
• History of chronic infection, such as Tuberculosis, AIDS, hepatitis
• CRP value \> 10 mg/L
• Women in pregnancy or lactation period

Sponsors & Collaborators

• Tianjin Anding Hospital: lead

Study Sites (1)

Tianjin Anding Hospital

Tianjin, Tianjin Municipality, 300222, China

RECRUITING

Related Publications (1)

• Yang C, Bosker FJ, Li J, Schoevers RA. N-acetylcysteine as add-on to antidepressant medication in therapy refractory major depressive disorder patients with increased inflammatory activity: study protocol of a double-blind randomized placebo-controlled trial. BMC Psychiatry. 2018 Sep 4;18(1):279. doi: 10.1186/s12888-018-1845-1.

  PMID: 30176835 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Chenghao Yang, Master

CONTACT

086 13752539531; yts83420@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2016
• First Posted: November 23, 2016
• Study Start: September 1, 2015
• Primary Completion: July 1, 2023
• Study Completion: September 1, 2023
• Last Updated: September 22, 2022

Record last verified: 2021-10

Locations

CN (1)