Bipolar DisorderPhase 4NCT02357290
Open-Label Study of N-Acetylcysteine in Children and Adolescents 5-17 With Bipolar Spectrum Disorders
A Phase 4 study testing Open-label Treatment with N-Acetylcysteine in people with Bipolar Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Children between the ages of 5-17 years old who have or display symptoms of emotional dysregulation (explosiveness, mood swings, irritability, and/or violent behavior) are invited to participate in a 12-week research study to determine the effectiveness and safety of the natural treatment N-acetylcysteine (NAC) for… Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Open-label Treatment with N-Acetylcysteine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to 24 Sep 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female subjects, 5-17 years of age
- Subjects must have a DSM-IV diagnosis of a bipolar spectrum disorder (type I, II, or Not Otherwise Specified) and currently display mixed, manic, or hypomanic symptoms (without psychotic features) according to clinical assessment based on the DSM-IV and confirmed with structured diagnostic interview
- Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator and to cooperate with all tests and examinations required by the protocol
- Subjects and their legal representatives must be considered reliable.
- Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must provide written consent and the subject must provide written assent.
- Subjects must have an initial score on the YMRS of at least 15.
Who cannot join
- Investigator and his/her immediate family (defined as the investigator's spouse, parent, child, grandparent, or grandchild)
- Serious or unstable illness including hepatic, rental, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
- Uncorrected hypothyroidism or hyperthyroidism
- History of sensitivity to N-acetylcysteine, a history of intolerance to N-acetylcysteine, or a non-responder after 2 months of treatment at adequate doses as determined by the clinician
- Severe allergies or multiple adverse drug reactions
- Current or past history of seizures
Show all 12Show fewer
- Active substance abusers, per clinician judgment
- Judged clinically to be at serious suicidal risk
- Current diagnosis of schizophrenia
- Pregnancy
- C-SSRS score ≥ 4
- IQ < 70
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Open-Label Study of N-Acetylcysteine in Children and Adolescents Ages 5-17 With Bipolar I, Bipolar II, and Bipolar Spectrum Disorder
Children between the ages of 5-17 years old who have or display symptoms of emotional dysregulation (explosiveness, mood swings, irritability, and/or violent behavior) are invited to participate in a 12-week research study to determine the effectiveness and safety of the natural treatment N-acetylcysteine (NAC) for children with emotional and behavioral problems. After undergoing a comprehensive evaluation by medical doctors with a specialty in this area, children who are found eligible to participate in this research study will be treated with NAC. Following the evaluation period, this research study requires 12 weekly visits, either in our office or over the phone, in an effort to closely monitor each child's response to the medication. Eligible participants will receive study-related evaluations and weekly study visits with our study doctors at no cost.
Read the detailed description
This will be a 12-week, open-label study of NAC in the treatment of bipolar disorder in children and adolescents. Subjects will include youth ages 5-17 years with a bipolar spectrum disorder (type I, II, or NOS), mixed, manic, or hypomanic state, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition DSM-5 (American Psychiatric Association, 2013). The primary outcome measures will be improvement in manic symptoms as measured by the Young Mania Rating Scale (YMRS) and improvement in depressive symptoms as measured by the Child Depression Rating Scale (CDRS).
Bipolar diagnoses will be made according to the DSM-5 in a clinical evaluation by a Child Psychiatrist and confirmed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Epidemiological Version (K-SADS-E)(Orvaschel, 1994). All subjects must have a YMRS score of at least 15. Only patients who are not responding to their current treatment regimen will be tapered from their medications; youth on concomitant psychiatric medications will be permitted to continue those medications as listed in the concomitant medication section.
- Conditions
- Bipolar Disorder
- Being tested
- Open-label Treatment with N-Acetylcysteine
- Keywords
- mania, temper tantrum, irritability, mood, bipolar
- Medical subject headings
- Bipolar Disorder, Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Open-label Treatment with N-AcetylcysteineDrug
| Study group | Role | What they receive |
|---|---|---|
| Open-label Treatment with NAC | Experimental | 12-week, open-label treatment with NAC. Subjects will be treated with the following dose:
Subjects ages 5-12:
Week 1: 900mg po daily Weeks 2+: 900mg po QAM, 900mg po QPM
Subjects ages 13-17:
Week 1: 900mg po daily Weeks 2-3: 900mg po QAM, 900mg po QPM Weeks 4+: 1800mg po QAM, 900mg po QPM
In Weeks 3-12 for subjects ages 13-17, we will encourage twice per day dosing, but we will permit daily dosing if needed for adherence. Receives: Drug: Open-label Treatment with N-Acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in the Young Mania Rating Scale (YMRS) Score
The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms.
Measured: Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12)
Secondary outcomes (1)
Mean Change in the Children's Depression Rating Scale (CDRS) Score
The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression.
Measured: Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2015 (estimated)
- Study startJan 2014
- Primary completion24 Sep 2018
- Study completion24 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Janet Wozniak, MD, Massachusetts General Hospital
- Investigators
- Janet Wozniak, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02357290
- Sponsor's protocol ID
- 2014P002011
- Status last verified
- Oct 2019
- First submitted
- 2 Feb 2015
- Last updated
- 4 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Wozniak J, DiSalvo M, Farrell A, Vaudreuil C, Uchida M, Ceranoglu TA, Joshi G, Cook E, Faraone SV, Biederman J. Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania. BMC Psychiatry. 2022 May 3;22(1):314. doi: 10.1186/s12888-022-03943-x.
PubMed 35505312
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label Study of N-Acetylcysteine in Children and Adolescents Ages 5-17 With Bipolar I, Bipolar II, and Bipolar Spectrum Disorder
- ClinicalTrials.gov ID
- NCT02357290
- Acronym / sponsor ID
- 2014P002011
- Conditions
- Bipolar Disorder
- Keywords
- mania, temper tantrum, irritability, mood, bipolar
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- 24 Sep 2018 (actual)
- Study completion
- 24 Sep 2018 (actual)
- First posted
- 6 Feb 2015 (estimated)
- Results
- Posted 4 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Children between the ages of 5-17 years old who have or display symptoms of emotional dysregulation (explosiveness, mood swings, irritability, and/or violent behavior) are invited to participate in a 12-week research study to determine the effectiveness and safety of the natural treatment N-acetylcysteine (NAC) for children with emotional and behavioral problems. After undergoing a comprehensive evaluation by medical doctors with a specialty in this area, children who are found eligible to participate in this research study will be treated with NAC. Following the evaluation period, this research study requires 12 weekly visits, either in our office or over the phone, in an effort to closely monitor each child's response to the medication. Eligible participants will receive study-related evaluations and weekly study visits with our study doctors at no cost.
Detailed description
This will be a 12-week, open-label study of NAC in the treatment of bipolar disorder in children and adolescents. Subjects will include youth ages 5-17 years with a bipolar spectrum disorder (type I, II, or NOS), mixed, manic, or hypomanic state, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition DSM-5 (American Psychiatric Association, 2013). The primary outcome measures will be improvement in manic symptoms as measured by the Young Mania Rating Scale (YMRS) and improvement in depressive symptoms as measured by the Child Depression Rating Scale (CDRS).
Bipolar diagnoses will be made according to the DSM-5 in a clinical evaluation by a Child Psychiatrist and confirmed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Epidemiological Version (K-SADS-E)(Orvaschel, 1994). All subjects must have a YMRS score of at least 15. Only patients who are not responding to their current treatment regimen will be tapered from their medications; youth on concomitant psychiatric medications will be permitted to continue those medications as listed in the concomitant medication section.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-label Treatment with NAC | Experimental | Drug: Open-label Treatment with N-Acetylcysteine12-week, open-label treatment with NAC. Subjects will be treated with the following dose: Subjects ages 5-12: Week 1: 900mg po daily Weeks 2+: 900mg po QAM, 900mg po QPM Subjects ages 13-17: Week 1: 900mg po daily Weeks 2-3: 900mg po QAM, 900mg po QPM Weeks 4+: 1800mg po QAM, 900mg po QPM In Weeks 3-12 for subjects ages 13-17, we will encourage twice per day dosing, but we will permit daily dosing if needed for adherence. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male or female subjects, 5-17 years of age
- Subjects must have a DSM-IV diagnosis of a bipolar spectrum disorder (type I, II, or Not Otherwise Specified) and currently display mixed, manic, or hypomanic symptoms (without psychotic features) according to clinical assessment based on the DSM-IV and confirmed with structured diagnostic interview
- Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator and to cooperate with all tests and examinations required by the protocol
- Subjects and their legal representatives must be considered reliable.
- Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must provide written consent and the subject must provide written assent.
Key exclusion criteria (12 listed)
- Investigator and his/her immediate family (defined as the investigator's spouse, parent, child, grandparent, or grandchild)
- Serious or unstable illness including hepatic, rental, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
- Uncorrected hypothyroidism or hyperthyroidism
- History of sensitivity to N-acetylcysteine, a history of intolerance to N-acetylcysteine, or a non-responder after 2 months of treatment at adequate doses as determined by the clinician
- Severe allergies or multiple adverse drug reactions
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 |
|---|---|---|
| Open-label Treatment with N-Acetylcysteine | Drug | Open-label Treatment with NAC |
Primary outcome
Mean Change in the Young Mania Rating Scale (YMRS) Score
Time frame: Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12)
The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms.
1 secondary outcome
Mean Change in the Children's Depression Rating Scale (CDRS) Score
Time frame: Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35505312Wozniak J, DiSalvo M, Farrell A, Vaudreuil C, Uchida M, Ceranoglu TA, Joshi G, Cook E, Faraone SV, Biederman J. Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania. BMC Psychiatry. 2022 May 3;22(1):314. doi: 10.1186/s12888-022-03943-x.
- Individual participant dataSharing planned: No
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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.
Janet Wozniak, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Open-label Treatment with N-Acetylcysteine in people with Bipolar Disorder, run by Massachusetts General Hospital at 1 site in United States.
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 6 inclusion and 12 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 4 Nov 2019. 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 United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Change in the Young Mania Rating Scale (YMRS) Score (time frame: Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 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 NCT02357290, 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 4 Nov 2019.