Bipolar DisorderPhase 2NACOSNCT02294591
NACOS - The Effect of N-acetylcystein for Depressive Symptoms in Patients Suffering From Bipolar Depression
A Phase 2 study testing N-acetylcysteine in people with Bipolar Disorder, run by Region Syddanmark at 1 site in Denmark.
Trial summary
This trial investigate add-on treatment with 3 g NAC vs. placebo in 20 weeks in patients suffering from bipolar depression. The primary outcome is MADRS-score, and the secondary outcomes are other psychometric evaluations oxidative stress biomarkers in urine. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- N-acetylcysteine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2014to Oct 2016
- Phase
- Phase 2
- 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients that meet the DSM-5 criteria of bipolar disorder type 1 or 2 (296-41-296.56 or 296.89) with at least one documented illness episode in the past six months, have had depressive symptoms at least 4 weeks before inclusion, MADRS ≥ 18 at baseline, have been sick at least 4 weeks, between 18-64 years, fertile women with a negative pregnant test at baseline, turtle women using safe contraception in the study period, and patients who have given informed consent.
Who cannot join
- Pregnant women, patients wishing pregnancy during the frame of the study, current suicidality, patients that have an intake of more than 500 mg NAC, 200 μm selenium, or 500 IU of vitamin E every day is excluded. Patients who are hypersensitive to histamine, patients who have had ECT-treatment within the last 4 weeks. Patients with recent bleeding in respiratory, asthma, epilepsy or allergy towards NAC. People who cannot speak or understand the Danish language, or have not give or withdrawn informed consent. If patients change diagnosis during the study, and the primary diagnosis is not bipolar affective disorder is the participant excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: NACOS - The Effect of N-acetylcystein for Depressive Symptoms in Patients Suffering From Bipolar Depression - A Double Blind Randomized Placebo-controlled Trial With Follow up
This trial investigate add-on treatment with 3 g NAC vs. placebo in 20 weeks in patients suffering from bipolar depression. The primary outcome is MADRS-score, and the secondary outcomes are other psychometric evaluations oxidative stress biomarkers in urine.
Read the detailed description
Bipolar depression can be extremely invalidating because of the depressive symptoms that results in decreased social functioning which reduces the quality of life. Bipolar depression is associated with three times longer duration of disorder period compared to mania. This emphasizes the importance of optimal treatment opportunities for this particular group.
Psychological treatments are often based on effective maintenance therapy, with limited evidence of acute bipolar depression. The effect of lithium in the acute phase of depression is low, and the use of valproate is still unclear in bipolar depression. Lamotrigine and other antipsychotics, has some efficacy in bipolar depression but have considerable tolerance issue. The most effective treatment is quetiapine and quetiapine XR, but this treatment is associated with side effects such as sedation, weight gain and dyslipidemia.
Individuals suffering from bipolar depression has a recognisable dysregulated oxidative mechanisms. Evidence indicates that GSH, which is the central antioxidant in brain are vulnerable to degradation. However, N-acetylcystine (NAC) improves the L-cysteine supply and leads to increase GSH in the brain.
A clinical randomized controlled study with 75 patients, showed a significant decreases in the primary outcome measure (MADRS-score) compared to the control group. Furthermore, were the general health status and function improved in NAC group.
This double-blinded randomized placebo controlled trial is conducted, to demonstrate the efficacy of NAC on depressive symptoms in patients suffering from bipolar depression, and examine the effect of add-on treatment of NAC on the level of oxidative stress, quality of life and functioning.
In total 87 participants will be included and recruited from The Mental Health Service from Region of Southern Denmark, to ensure sufficient participants in the study.
The trial will run for a 24 weeks period for each participant. Participants in the study will be randomized to either NAC and standard treatment, or placebo and standard treatment for 20 weeks, followed by a 4-week follow-up period.
This trial is the first of its kind, analysing the level of oxidative stress in both blood and urine samples among people suffering from bipolar depression, to examine the add-on effect of NAC treatment.
The study receive academic and scientific advice from Ramus W. Licht, professor, ph.d, and clinical advice from Henrik E. Poulsen, professor, dr.med. This is two international professors in respectively bipolar disorder and oxidative stress. Furthermore, there is an international corporation and support from professor Michael Berk and dr. Olivia Dean from Deakin University, Australia, which have performed the previously trials concerning NAC treatment and bipolar depression.
The study medication has low side effects and low cost, both advantages, which are desirable for especially this vulnerable group of people. This trial may contribute to optimal treatment opportunities for people suffering from bipolar depression, and possibly other psychiatric patients as well.
- Conditions
- Bipolar Disorder
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- Bipolar Disorder, Depression, Acetylcystein, Oxidative Stress, Urine
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC
Add-on treatment of NAC
PlaceboDrug
Add-on treatment of placebo
| Study group | Role | What they receive |
|---|---|---|
| NAC group | Active comparator | Receiving N-acetylcysteine as add-on treatment Receives: Drug: N-acetylcysteine |
| Placebo group | Placebo comparator | Receiving placebo as add-on treatment Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The total score of MADRS
Measured: Change from baseline MADRS-score at 20 weeks
Secondary outcomes (6)
The total score of MES
Measured: Change from baseline MES-score at 20 weeks
The total score of WHO-5
Measured: Change from baseline WHO-5-score at 20 weeks
The total score of GAF-S
Measured: Change from baseline GAF-S-score at 20 weeks
The total score of GAF-F
Measured: Change from baseline GAF-F-score at 20 weeks
The total score of YMRS
Measured: Change from baseline YMRS-score at 20 weeks
The measurement of oxidative stress in biological material (urine)
Measured: Change from baseline oxidative stress measurement at 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study startNov 2014
- Primary completionOct 2016
- Study completionOct 2016
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 Bipolar DisorderStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Syddanmark
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Connie Thuree Nielsen, consultant, MD, ph.d, Region Syddanmark
- Investigators
- Connie T. Nielsen, Ph.D, Principal investigator, Mental Health Service, Esbjerg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02294591
- Sponsor's protocol ID
- 35664
- Other IDs
- 2012-004483-22
- Acronym
- NACOS
- Status last verified
- Nov 2016
- First submitted
- 6 Nov 2014
- Last updated
- 28 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ellegaard PK, Licht RW, Poulsen HE, Nielsen RE, Berk M, Dean OM, Mohebbi M, Nielsen CT. Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol). Int J Bipolar Disord. 2018 Apr 5;6(1):11. doi: 10.1186/s40345-018-0117-9.
PubMed 29619634
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NACOS - The Effect of N-acetylcystein for Depressive Symptoms in Patients Suffering From Bipolar Depression - A Double Blind Randomized Placebo-controlled Trial With Follow up
- ClinicalTrials.gov ID
- NCT02294591
- Acronym / sponsor ID
- NACOS / 35664
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Disorder, Depression, Acetylcystein, Oxidative Stress, Urine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Region SyddanmarkUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 19 Nov 2014 (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.
This trial investigate add-on treatment with 3 g NAC vs. placebo in 20 weeks in patients suffering from bipolar depression. The primary outcome is MADRS-score, and the secondary outcomes are other psychometric evaluations oxidative stress biomarkers in urine.
Detailed description
Bipolar depression can be extremely invalidating because of the depressive symptoms that results in decreased social functioning which reduces the quality of life. Bipolar depression is associated with three times longer duration of disorder period compared to mania. This emphasizes the importance of optimal treatment opportunities for this particular group.
Psychological treatments are often based on effective maintenance therapy, with limited evidence of acute bipolar depression. The effect of lithium in the acute phase of depression is low, and the use of valproate is still unclear in bipolar depression. Lamotrigine and other antipsychotics, has some efficacy in bipolar depression but have considerable tolerance issue. The most effective treatment is quetiapine and quetiapine XR, but this treatment is associated with side effects such as sedation, weight gain and dyslipidemia.
Individuals suffering from bipolar depression has a recognisable dysregulated oxidative mechanisms. Evidence indicates that GSH, which is the central antioxidant in brain are vulnerable to degradation. However, N-acetylcystine (NAC) improves the L-cysteine supply and leads to increase GSH in the brain.
A clinical randomized controlled study with 75 patients, showed a significant decreases in the primary outcome measure (MADRS-score) compared to the control group. Furthermore, were the general health status and function improved in NAC group.
This double-blinded randomized placebo controlled trial is conducted, to demonstrate the efficacy of NAC on depressive symptoms in patients suffering from bipolar depression, and examine the effect of add-on treatment of NAC on the level of oxidative stress, quality of life and functioning.
In total 87 participants will be included and recruited from The Mental Health Service from Region of Southern Denmark, to ensure sufficient participants in the study.
The trial will run for a 24 weeks period for each participant. Participants in the study will be randomized to either NAC and standard treatment, or placebo and standard treatment for 20 weeks, followed by a 4-week follow-up period.
This trial is the first of its kind, analysing the level of oxidative stress in both blood and urine samples among people suffering from bipolar depression, to examine the add-on effect of NAC treatment.
The study receive academic and scientific advice from Ramus W. Licht, professor, ph.d, and clinical advice from Henrik E. Poulsen, professor, dr.med. This is two international professors in respectively bipolar disorder and oxidative stress. Furthermore, there is an international corporation and support from professor Michael Berk and dr. Olivia Dean from Deakin University, Australia, which have performed the previously trials concerning NAC treatment and bipolar depression.
The study medication has low side effects and low cost, both advantages, which are desirable for especially this vulnerable group of people. This trial may contribute to optimal treatment opportunities for people suffering from bipolar depression, and possibly other psychiatric patients as well.
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 | Active comparator | Drug: N-acetylcysteineReceiving N-acetylcysteine as add-on treatment |
| Placebo group | Placebo comparator | Drug: PlaceboReceiving placebo as add-on treatment |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Patients that meet the DSM-5 criteria of bipolar disorder type 1 or 2 (296-41-296.56 or 296.89) with at least one documented illness episode in the past six months, have had depressive symptoms at least 4 weeks before inclusion, MADRS ≥ 18 at baseline, have been sick at least 4 weeks, between 18-64 years, fertile women with a negative pregnant test at baseline, turtle women using safe contraception in the study period, and patients who have given informed consent.
Key exclusion criteria (1 listed)
- Pregnant women, patients wishing pregnancy during the frame of the study, current suicidality, patients that have an intake of more than 500 mg NAC, 200 μm selenium, or 500 IU of vitamin E every day is excluded. Patients who are hypersensitive to histamine, patients who have had ECT-treatment within the last 4 weeks. Patients with recent bleeding in respiratory, asthma, epilepsy or allergy towards NAC. People who cannot speak or understand the Danish language, or have not give or withdrawn informed consent. If patients change diagnosis during the study, and the primary diagnosis is not bipolar affective disorder is the participant excluded.
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: NACAdd-on treatment of NAC | Drug | NAC group |
| PlaceboAdd-on treatment of placebo | Drug | Placebo group |
Primary outcome
The total score of MADRS
Time frame: Change from baseline MADRS-score at 20 weeks
6 secondary outcomes
The total score of MES
Time frame: Change from baseline MES-score at 20 weeks
The total score of WHO-5
Time frame: Change from baseline WHO-5-score at 20 weeks
The total score of GAF-S
Time frame: Change from baseline GAF-S-score at 20 weeks
The total score of GAF-F
Time frame: Change from baseline GAF-F-score at 20 weeks
The total score of YMRS
Time frame: Change from baseline YMRS-score at 20 weeks
The measurement of oxidative stress in biological material (urine)
Time frame: Change from baseline oxidative stress measurement at 20 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Derived from this study: PubMed 29619634Ellegaard PK, Licht RW, Poulsen HE, Nielsen RE, Berk M, Dean OM, Mohebbi M, Nielsen CT. Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol). Int J Bipolar Disord. 2018 Apr 5;6(1):11. doi: 10.1186/s40345-018-0117-9.
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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.
Connie T. Nielsen, Ph.D principal investigator
Mental Health Service, Esbjerg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine in people with Bipolar Disorder, run by Region Syddanmark at 1 site in Denmark.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 28 Nov 2016. 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 Denmark. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The total score of MADRS (time frame: Change from baseline MADRS-score at 20 weeks). 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 NCT02294591, 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 28 Nov 2016.