A Pilot Trial of Tapering Antipsychotics for Patients in Remitted Psychosis Co-administering With N-Acetylcysteine

August 6, 2024 updated by: National Taiwan University Hospital

Tapering Antipsychotics in Patients With Remitted Psychosis: From Bedside to Bench Employing Animal Model and N-Acetylcysteine Study and Back to Bedside

The investigators are going to observe if add-on of n-acetylcysteine (NAC) 1200 or 2400 mg/d during tapering of antipsychotics in patients with remitted psychosis can help to reduce the pre-requisite of stabilization to 3 months (compared to the 6 months prerequisite of a previous Guided Antipsychotic Reduction to Minimum Effective Dose (GARMED) trial,) smoothly, without increased risk of relapse or frequency of adverse events compared to the 2-year results of the GARMED trial

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Trial procedure

  • Pretreatment: more instructions were delivered regarding the extent and the tempo of dose reduction, warning signal of relapse, timing to call for help if in need to resume rescue dose, and a shared decision-making process during tapering. Pre-treatment of NAC 1200 mg/d will be given for 1-2 weeks and then titrated up to 2400 mg/d to test tolerability. Patients will stay at either dose throughout the remaining of the course as preferable.
  • Dose tapering schedule: In the beginning, no more than one-quarter of the baseline antipsychotic dose will be reduced at a time. Patients need to be monitored every 4 weeks (or 1 month) by phone or in person. If they can maintain stabilized for 12 weeks (or 3 months) in a reduced dose, they can take next tapering of no more than one quarter of their current dose again, yielding 9/16 (3/4x3/4) of baseline dose. The subsequent dose reduction will be a reiteration of the previous step, cutting off one-quarter of the current dose following the formula (3/4) powered by n, rather than cutting off another 1/4 of the initial dose. The processes will be reiterated for 4 steps for one year.
  • Conditions during tapering: Noteworthily, when the patient is eligible to consider next dose reduction, he or she is empowered to take shared decision-making as they might opt to stay at their current dose for a more extended time for any reason. Patients can reach the study team during the course whenever they felt unsure if any relapse sign might be re-emerging. As needed use of benzodiazepines or hypnotics will be allowed to help control suspected signs of relapse. Patients will be supervised to stay at current dose for a longer term or even re-escalate to previous higher dose if any sign of suspected relapse re-emerges, and then will be closely monitored if their symptoms can be stabilized within 2 weeks.
  • Defining relapse: If a patient's recurrent psychotic symptoms cannot be controlled (any PANSS score > 3 in P1, P2, P3, G5, or G9) within 2 weeks under an antipsychotic dose equal to their baseline dose, the patient will be designated as having a relapse.
  • Practicability of dosing: The actual dose taken would not always be precisely the number calculated by the formula (3/4)n, as it was impractical to cut off a quarter or even smaller piece of a tablet for daily dosing. Several versions of intermittent or irregular dosing schedules have been generated to meet the needs.
  • Extent of dose reduction: The percentage of doses reduced at a designated time point will be calculated by the following formula: [1- (current dose)/(baseline dose)]x100%.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Both male and female outpatients or patients at psychiatric daycare service
  2. Age 18-60 years old at the time of screening
  3. A diagnosis of schizophrenia, schizophreniform disorder, psychosis NOS, based on the DSM-5 criteria
  4. With a Positive and Negative Syndrome Scale (PANSS), score < 3 in all 3 positive symptoms (P1: delusion, P2: conceptual disorganization, P3: hallucination) and 2 general symptoms (G9: unusual thought, G5: mannerism and posturing) for at least 3 months
  5. With a PANSS score < 4 in all 3 negative symptoms (N1: blunted affect, N4: social withdrawal, N6: lack of spontaneity/flow in conversation) for at least 3 months
  6. Currently receiving antipsychotic treatment at a fixed dose for at least 3 months, including long-acting injectable antipsychotic
  7. No revised use of benzodiazepines, antidepressants, anticholinergics, or other concomitant medications during the past 3 months

Exclusion Criteria:

  1. A score of 5 or more on any of the 30 PANSS rating items at screening
  2. Admission to the acute psychiatric unit during the past 6 months
  3. A change in dose of current antipsychotic medication in recent 3 months
  4. Concomitant use of mood stabilizers, such as lithium, valproic acid, or other anti-epileptic drugs
  5. Mental retardation known as IQ below 70 prior to the diagnosis of schizophrenia
  6. A history of pervasive mental disorder or bipolar disorder
  7. A medical condition with significant cognitive sequelae
  8. A history of substance dependence during the past 6 months
  9. Currently in pregnancy or breastfeeding
  10. A history of allergy to N-Acetylcysteine
  11. Patient with phenylketonuria ( because the Actein Effervescent Tablet 600 mg/tab contains aspartame)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NAC add-on 1
NAC add-on with 1200 mg/d
Drug: N-Acetylcysteine
regular dose or high dose add-on
Other Names:
  • N-Acetylcysteine 2400 mg/d
Active Comparator: NAC add-on 2
NAC add-on with 2400 mg/d
Drug: N-Acetylcysteine
regular dose or high dose add-on
Other Names:
  • N-Acetylcysteine 2400 mg/d

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Relapse rate (%)
Time Frame: 1 year
If a patient's recurrent psychotic symptoms cannot be controlled (any PANSS score > 3 in P1, P2, P3, G5, or G9) within 2 weeks under an antipsychotic dose equal to their baseline dose, the patient will be designated as having a relapse
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Extent of dose reduction (%)
Time Frame: 1 year
The percentage of doses reduced at a designated time point will be calculated by the formula: [1- (current dose)/(baseline dose)]x100%
1 year
Clinical severity: symptoms
Time Frame: 1 year
Positive and Negative Syndrome Scale (PANSS) (1 to 7, 1: normal; 7: profound severity)
1 year
Clinical severity: global
Time Frame: 1 year
Clinical Global Impression of Severity (CGI-S) (1 to 7, 1: no illness; 7: most severe)
1 year
Personal and Social Functioning
Time Frame: 1 year
Personal and Social Performance scale (PSP) (0-100, worst to best)
1 year
Self-report of subjective wellbeing
Time Frame: 1 year
EuroQoL-5D visual analogue scale (EQ-5D-VAS) (0-100, worst to best)
1 year
Self-report of Quality of Life
Time Frame: 1 year
Mandarin Chinese version of the WHOQOL-BREF (1~5, 1: very dissatisfied; 5: very satisfied)
1 year

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Qualitative measurements by semi-structured interview
Time Frame: 1 year
At each time point of shared decision-making regarding whether to taper down dose or not, we will conduct a semi-structure interview to explore patient's key considerations, such as psychosocial issues, soundness of supportive system, and self-assessed risk of relapse, which prompt the patient to feel comfortable about continuing tapering, or to halt at current dose for a longer term.
1 year
Self-report of Medication Adherence
Time Frame: 1 year
5-point Likert scale for medication adherence (1: < 20%; 2: 20~40%; 3: 40~60%; 4: 60~80%; 5: > 80%)
1 year
Self-report of Medication Satisfaction
Time Frame: 1 year
7-point Likert scale for medication satisfaction (1: most dissatisfied; 7: most satisfied)
1 year
Adverse events
Time Frame: 1 year
checklist of Udvalg for Kliniske Undersogelser (UKU) Side-effects Rating Scale
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Taiwan University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chen-Chung Liu, MD, PhD, National Taiwan University, College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202401210MIND
  • NSTC 113-2314-B-002-184-MY3 (Other Grant/Funding Number: National Science and Technology Council (NSTC), Taiwan)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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