Major Depressive DisordersNCT02972398
N-Acetyl Cysteine Supplementation in Therapy Refractory Major Depressive Disorders
A study testing N-acetylcysteine in people with Major Depressive Disorders, run by Tianjin Anding Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorders
- What is being tested?
- N-acetylcysteine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- Sep 2015to Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Tianjin Anding Hospital
Tianjin, Tianjin Municipality, 300222
Jie Li, Doctor, +86 022 88188006, tjlijie3827@163.com
About this study
Official title: N-Acetyl Cysteine add-on to Antidepressant Medication in Therapy Refractory Major Depressive Disorder Patients With Increased Inflammatory Activity
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.
Read the 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
- Being tested
- N-acetylcysteine, placebo comparator of N-acetylcysteine
- Keywords
- treatment resistant depression, N-Acetyl Cysteine, inflammation mediators, oxidative stress, brain imaging
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called YiWeiShi
Participants of interventional group receive 1000mg N-acetylcysteine twice daily for 12 weeks.
placebo comparator of N-acetylcysteineDrug
Participants of placebo group receive placebo comparator matching with N-acetylcysteine twice daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: placebo comparator of N-acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
We also look at whether daily oral NAC treatment will still have measurable effects on HAMD-17 score at 8 weeks follow-up after discontinuation of NAC treatment.
Measured: baseline, Week 14,16,18,and 20.
The effects of augmentation treatment with NAC on scores in Beck Anxiety Inventory (BAI)
Measured: 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)
Measured: 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)
Measured: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on scores in Montreal Cognitive Assessment (MoCA)
Measured: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on local brain activity (fMRI and DTI)
Measured: baseline, the end of week 12.
The effects of augmentation treatment with NAC on a range of biomarkers representing the alleged underlying pathophysiological mechanisms
biomarkers associated with inflammation, oxidative stress, and neurogenesis in sample of serum and urine.
Measured: baseline, the end of the week 12 and 20
Assessments the side effects measured with Checklist of 52 Somatic Items (CSI)
Measured: baseline, Week 4,8,12,16,and 20.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2016 (estimated)
- Study startSep 2015
- Primary completionJul 2023 (estimated)
- Study completionSep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Anding Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02972398
- Sponsor's protocol ID
- NAC-2015-TJAH
- Status last verified
- Oct 2021
- First submitted
- 12 Nov 2016
- Last updated
- 22 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 30176835
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-Acetyl Cysteine add-on to Antidepressant Medication in Therapy Refractory Major Depressive Disorder Patients With Increased Inflammatory Activity
- ClinicalTrials.gov ID
- NCT02972398
- Acronym / sponsor ID
- NAC-2015-TJAH
- Conditions
- Major Depressive Disorders
- Keywords
- treatment resistant depression, N-Acetyl Cysteine, inflammation mediators, oxidative stress, brain imaging
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Tianjin Anding HospitalUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Sep 2023 (estimated)
- First posted
- 23 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NAC group | Experimental | Drug: N-acetylcysteineParticipants 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) |
| Placebo group | Placebo comparator | Drug: placebo comparator of N-acetylcysteineParticipants 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) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: YiWeiShiParticipants of interventional group receive 1000mg N-acetylcysteine twice daily for 12 weeks. | Drug | NAC group |
| placebo comparator of N-acetylcysteineParticipants of placebo group receive placebo comparator matching with N-acetylcysteine twice daily for 12 weeks. | Drug | Placebo group |
Primary outcome
The change from baseline Hamilton Depression Rating Scale (HAMD)-17 items at week2,4,6,8,10,and 12.
Time frame: baseline, Week 2,4,6,8,10, 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.
8 secondary outcomes
The change from baseline HAMD-17 items at week14,16,18,and 20.
Time frame: baseline, Week 14,16,18,and 20.
The effects of augmentation treatment with NAC on scores in Beck Anxiety Inventory (BAI)
Time frame: 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)
Time frame: 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)
Time frame: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on scores in Montreal Cognitive Assessment (MoCA)
Time frame: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on local brain activity (fMRI and DTI)
Time frame: baseline, the end of week 12.
The effects of augmentation treatment with NAC on a range of biomarkers representing the alleged underlying pathophysiological mechanisms
Time frame: baseline, the end of the week 12 and 20
Assessments the side effects measured with Checklist of 52 Somatic Items (CSI)
Time frame: baseline, Week 4,8,12,16,and 20.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Derived from this study: PubMed 30176835Yang 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-acetylcysteine in people with Major Depressive Disorders, run by Tianjin Anding Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chenghao Yang, Master (086 13752539531, yts83420@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change from baseline Hamilton Depression Rating Scale (HAMD)-17 items at week2,4,6,8,10,and 12. (time frame: baseline, Week 2,4,6,8,10, and 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02972398, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022; AzTrials last refreshed its copy on 7 Nov 2026.