Adverse EffectsPhase 4NCT00707915
Effects of Discontinuation of Benzodiazepine-derivative Hypnotics on Cognitive and Motor Functions in Elderly Persons
A Phase 4 study testing Drug: Benzodiazepine (listed out below) in people with Adverse Effects, run by Minamihanno Hospital at 1 site in Japan.
Trial summary
Benzodiazepines (BZDs) have been reported to cause negative impacts on motor as well as cognitive functions, which in turn could result in lethal incidents including falls especially in the elderly. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Adverse Effects
- What is being tested?
- Drug: Benzodiazepine (listed out below)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteJapan
- Study dates
- Jan 2008to Jul 2010
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants of any race or ethnicity with any psychiatric diagnosis
- Age of 50 and older
- Having been treated with an BZD-derivative hypnotic drug at a steady dose for at least 4 weeks
Who cannot join
- Incapacity to follow the instructions.
- Unstable physical illness or significant neurological disorder
- Psychiatric concerns raised by the physician of record regarding participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Discontinuation of Benzodiazepine-derivative Hypnotics on Cognitive and Motor Functions in Elderly Persons: a Pilot Study
Benzodiazepines (BZDs) have been reported to cause negative impacts on motor as well as cognitive functions, which in turn could result in lethal incidents including falls especially in the elderly. This notwithstanding, few trials have evaluated a feasibility and benefits of discontinuing BZD-derivative hypnotics in a systematic manner in this frail population. In this 8-week open-label study, we examined changes in motor and cognitive functions following the discontinuation of BZD hypnotics in older persons.
OBJECTIVES \& HYPOTHESES
Read more
- Primary Objective The primary objective is to examine the feasibility of discontinuing BZD-derivative hypnotics in older people.
- Secondary Objectives
- One of the secondary objectives is to examine the magnitude of discontinuing BZD-derivative hypnotics in the stability of body.
- Another secondary objective is to examine the magnitude of discontinuing BZD-derivative hypnotics in cognitive function.
Hypotheses
- More than 80% of the participants will complete and tolerate all the study procedures.
2a. Participants will show an improvement in the stability of body. 2b. Participants will show an improvement in the cognitive function globally as well as specifically in attention.
Read the detailed description
Benzodiazepines (BZDs) have been reported to cause negative impacts on motor as well as cognitive functions, which in turn could result in lethal incidents including falls especially in the elderly. This notwithstanding, few trials have evaluated a feasibility and benefits of discontinuing BZD-derivative hypnotics in a systematic manner in this frail population. In this study, we examined changes in motor and cognitive functions following the discontinuation of BZD hypnotics in older persons.
In this 8-week open-label study, subjects aged 50 or older who receive BZD as a hypnotic and do not have any unstable physical illness, or neurological disorder will be recruited. The BZD dose will be discontinued in 4 weeks by a weekly 25% reduction.
Following assessments will be performed at baseline 12 hours postdose and at endpoint: the Clinical Stabilometric Platform (CSP), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Critical Flicker Fusion Test (CFF), the Leeds Sleep Evaluation Questionnaire (LSEQ). The CSP measures the stability of body, with the eyes opened or closed.
All psychotropic agents other than the BZD-derivative hypnotics will be kept constant throughout the study.
The dose reduction will be terminated if any of the following conditions are fulfilled:
- Clinical worsening in sleep defined as a CGI-Global Improvement score of 7
- Participant's request
- Clinical decision on the part of the physician of record or independent consulting physician In the event that a participant needs a dose increment for anxiety and insomnia, the dose will be increased back to the previous dose, and they will be followed for the rest of the study period. In addition, the use of trazodone (25-100 mg/day) will be allowed anytime throughout the study period.
- Conditions
- Adverse Effects
- Being tested
- Drug: Benzodiazepine (listed out below)
- Keywords
- aged, benzodiazepines, hypnotics, cognition, posture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: Benzodiazepine (listed out below)Drug
The benzodiazepine (BZD) dose will be discontinued in 4 weeks by a weekly 25% reduction. BZD-derivative hypnotics will include brotizolam, flunitrazepam, etizolam, quazepam, estazolam, nitrazepam, flurazepam, and diazepam.
All psychotropic agents other than the BZD-derivative hypnotics will be kept constant throughout the study. In addition, the use of trazodone (25-100 mg/day) will be allowed anytime throughout the study period. Subjects will be observed for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Dose reduction | Experimental | The benzodiazepine dose will be discontinued in 4 weeks by a weekly 25% reduction. Participants will be observed for 8 weeks. Receives: Drug: Drug: Benzodiazepine (listed out below) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Completion Rate
The number of subjects who have successfully completed dose-reduction and all the assessments scheduled until week 8 divided by the total number of enrolled subjects
Measured: 8 weeks
Secondary outcomes (5)
A Change in a Total Scale Score in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Japanese Version, From Baseline to Week 8.
This brief test is to assess areas of cognitive functioning and profile impairment across domains with 12 subtests, including: List Learning, Story Memory, Figure Copy, Line Orientation, Digit Span, Coding, Picture Naming, Semantic Fluency, List Recall, List Recognition, Story Recall, and Figure Recall. This assessment is repeatable and not subject to practice effects. A total scale score ranges between 40 and 160; a higher score indicates better cognitive function. A change in the score between the baseline and week 8 is defined as a secondary outcome measure.
Measured: Baseline and week 8
Clinical Stabilometric Platform (CSP)
CSP (ANIMA® GS-7, Tokyo) measures a total length of the trunk motion by varying the resistance applied to the platform for 30 seconds with eyes closed with feet together. Change in the total length of the trunk motion from baseline to week 8 will be recorded.
Measured: Baseline and week 8
Critical Flicker Fusion Test (CFF)
The CFF threshold has been regarded as a functional measure of psychomotor function. Sub-threshold intermittent light is perceived as a flicker. If the frequency is gradually increased, the flicker becomes gradually less distinct until it is finally perceived as a continuous light (fusion threshold). The device (T.K.K.501c) provides luminance with a mean intensity of 500Lux±10% and a range of frequency of 20-60Hz. A change in the critical fusion frequency from baseline to week 8 will be recorded.
Measured: Baseline and week 8
Leeds Sleep Evaluation Questionnaire (LSEQ)
The LSEQ comprises 10 self-rating 100-mm-line analogue questions regarding changes in the quality of sleep and early morning behavior, following any given intervention. Scores range between 0 and 100. Scores beneath 50 indicate better sleep. This will be performed at week 8.
Measured: Week 8
Clinical Global Impression (CGI)
The CGI rating scales are commonly used measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of patients with mental disorders (Guy, W., 1976). The CGI - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. This will be performed at week 8.
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2008 (estimated)
- Study startJan 2008
- Primary completionJul 2010
- Study completionJul 2010
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.
- Other trials for Adverse EffectsStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Minamihanno Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kenichi Tsunoda, MD, Principal investigator, Minamihanno Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00707915
- Sponsor's protocol ID
- MH0001
- Status last verified
- Mar 2012
- First submitted
- 27 Jun 2008
- Last updated
- 27 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Discontinuation of Benzodiazepine-derivative Hypnotics on Cognitive and Motor Functions in Elderly Persons: a Pilot Study
- ClinicalTrials.gov ID
- NCT00707915
- Acronym / sponsor ID
- MH0001
- Conditions
- Adverse Effects
- Keywords
- aged, benzodiazepines, hypnotics, cognition, posture
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Minamihanno HospitalUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 1 Jul 2008 (estimated)
- Results
- Posted 26 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Benzodiazepines (BZDs) have been reported to cause negative impacts on motor as well as cognitive functions, which in turn could result in lethal incidents including falls especially in the elderly. This notwithstanding, few trials have evaluated a feasibility and benefits of discontinuing BZD-derivative hypnotics in a systematic manner in this frail population. In this 8-week open-label study, we examined changes in motor and cognitive functions following the discontinuation of BZD hypnotics in older persons.
OBJECTIVES \& HYPOTHESES
- Primary Objective The primary objective is to examine the feasibility of discontinuing BZD-derivative hypnotics in older people.
- Secondary Objectives
- One of the secondary objectives is to examine the magnitude of discontinuing BZD-derivative hypnotics in the stability of body.
- Another secondary objective is to examine the magnitude of discontinuing BZD-derivative hypnotics in cognitive function.
Hypotheses
- More than 80% of the participants will complete and tolerate all the study procedures.
2a. Participants will show an improvement in the stability of body. 2b. Participants will show an improvement in the cognitive function globally as well as specifically in attention.
Detailed description
Benzodiazepines (BZDs) have been reported to cause negative impacts on motor as well as cognitive functions, which in turn could result in lethal incidents including falls especially in the elderly. This notwithstanding, few trials have evaluated a feasibility and benefits of discontinuing BZD-derivative hypnotics in a systematic manner in this frail population. In this study, we examined changes in motor and cognitive functions following the discontinuation of BZD hypnotics in older persons.
In this 8-week open-label study, subjects aged 50 or older who receive BZD as a hypnotic and do not have any unstable physical illness, or neurological disorder will be recruited. The BZD dose will be discontinued in 4 weeks by a weekly 25% reduction.
Following assessments will be performed at baseline 12 hours postdose and at endpoint: the Clinical Stabilometric Platform (CSP), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Critical Flicker Fusion Test (CFF), the Leeds Sleep Evaluation Questionnaire (LSEQ). The CSP measures the stability of body, with the eyes opened or closed.
All psychotropic agents other than the BZD-derivative hypnotics will be kept constant throughout the study.
The dose reduction will be terminated if any of the following conditions are fulfilled:
- Clinical worsening in sleep defined as a CGI-Global Improvement score of 7
- Participant's request
- Clinical decision on the part of the physician of record or independent consulting physician In the event that a participant needs a dose increment for anxiety and insomnia, the dose will be increased back to the previous dose, and they will be followed for the rest of the study period. In addition, the use of trazodone (25-100 mg/day) will be allowed anytime throughout the study period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose reduction | Experimental | Drug: Drug: Benzodiazepine (listed out below)The benzodiazepine dose will be discontinued in 4 weeks by a weekly 25% reduction. Participants will be observed for 8 weeks. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female participants of any race or ethnicity with any psychiatric diagnosis
- Age of 50 and older
- Having been treated with an BZD-derivative hypnotic drug at a steady dose for at least 4 weeks
Key exclusion criteria (3 listed)
- Incapacity to follow the instructions.
- Unstable physical illness or significant neurological disorder
- Psychiatric concerns raised by the physician of record regarding participation in the study.
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 |
|---|---|---|
| Drug: Benzodiazepine (listed out below)The benzodiazepine (BZD) dose will be discontinued in 4 weeks by a weekly 25% reduction. BZD-derivative hypnotics will include brotizolam, flunitrazepam, etizolam, quazepam, estazolam, nitrazepam, flurazepam, and diazepam. All psychotropic agents other than the BZD-derivative hypnotics will be kept constant throughout the study. In addition, the use of trazodone (25-100 mg/day) will be allowed anytime throughout the study period. Subjects will be observed for 8 weeks. | Drug | Dose reduction |
Primary outcome
Completion Rate
Time frame: 8 weeks
The number of subjects who have successfully completed dose-reduction and all the assessments scheduled until week 8 divided by the total number of enrolled subjects
5 secondary outcomes
A Change in a Total Scale Score in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Japanese Version, From Baseline to Week 8.
Time frame: Baseline and week 8
Clinical Stabilometric Platform (CSP)
Time frame: Baseline and week 8
Critical Flicker Fusion Test (CFF)
Time frame: Baseline and week 8
Leeds Sleep Evaluation Questionnaire (LSEQ)
Time frame: Week 8
Clinical Global Impression (CGI)
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kenichi Tsunoda, MD principal investigator
Minamihanno 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 Drug: Benzodiazepine (listed out below) in people with Adverse Effects, run by Minamihanno Hospital at 1 site in Japan.
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 3 inclusion and 3 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 27 Mar 2012. 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 Japan. 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 26 Mar 2012). 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?
Completion Rate (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Mar 2012; AzTrials last refreshed its copy on 8 Nov 2026.