N-Acetyl Cysteine Supplementation in Therapy Refractory Major Depressive Disorders

NCT ID: NCT02972398

Last Updated: 2022-09-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2023-09-30

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.

Detailed Description

It's a double-blind randomised placebo controlled antidepressant augmentation study with 12-week treatment and 8-week follow up. Its purpose is to investigate antidepressant efficacy and safety of NAC in patients with treatment resistant depression (TRD) defined as insufficient response to 1 or more antidepressants given for at least 6 weeks and in an adequate dose, displaying increased peripheral inflammatory activity and moderate to severe depression. Apart from studying the effects of NAC on depression severity, the secondary outcomes are to examine a range of biomarkers related to potentially important underlying mechanisms such as oxidative stress and inflammatory activity and to evaluate the effects on brain functioning (fMRI) and on white matter integrity (DTI). Scale assessments are performed in the week preceding initiation of treatment, during the treatment period, at the end of the treatment period and at 8-week follow up. Neuro-imaging is performed before the treatment starts and in week 12, before the study medication is terminated. Collection of blood and morning urine only takes place at three time points, in the week preceding initiation of treatment, closely before tapering off the study medication and at the end of 8-week follow up. This study is hoped to show that NAC perform positive effects on those aspects mentioned above.

Conditions

Major Depressive Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NAC group

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)

Group Type: EXPERIMENTAL

N-acetylcysteine

Intervention Type: DRUG

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

Placebo group

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)

Group Type: PLACEBO_COMPARATOR

placebo comparator of N-acetylcysteine

Intervention Type: DRUG

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

Interventions

N-acetylcysteine

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

Intervention Type: DRUG

placebo comparator of N-acetylcysteine

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

Intervention Type: DRUG

Other Intervention Names

YiWeiShi

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Anding Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tianjin Anding Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Chenghao Yang, Master

Role: CONTACT

yts83420@163.com

086 13752539531

Facility Contacts

Jie Li, Doctor

Role: primary

tjlijie3827@163.com

+86 022 88188006

References

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.

Reference Type: DERIVED

PMID: 30176835 (View on PubMed)

Other Identifiers

NAC-2015-TJAH

Identifier Type: -

Identifier Source: org_study_id