Bipolar II DisorderPhase 2/3NCT04035798
add-on Low Dose Memantine in Middle-to-old Aged Bipolar II Disorder Patients
A Phase 2/3 study of Bipolar II Disorder, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
The investigators hypothesized that add-on memantine (MM) 5 mg/day may reduce chronic inflammation, and subsequently improve neuro-progression process and cognitive function in middle-to-old aged bipolar II disorder (BP-II) patients. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Bipolar II Disorder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2019to 31 Jul 2022
- Phase
- Phase 2/3
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent by patient or legal representative.
- Male or female patient aged ≧40 years.
- A diagnosis of bipolar II disorder according to Diagnostic and Statistical Manual of Mental Disorders criteria made by a specialist in psychiatry.
- Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.
Who cannot join
- The presence of any of the following will exclude a patient from study enrollment:
- Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.
- Females who are pregnant or lactation.
- Comorbid with substance-related disorders, borderline personality disorder, schizophrenia, mental retardation, dementia or other major psychiatric disorders. But comorbid with anxiety disorder or tobacco use disorder is not an exclusion criteria.
- Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.
- History of allergy or intolerable side effects of valproic acid, memantine, risperidone, fluoxetine, lorazepam.
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- History of receiving electroconvulsive therapy.
- Levels of total bilirubin, aspartate aminotransferase(AST)、alanine transaminase(ALT) were elevated more than twice of normal range. Levels of Blood urea nitrogen(BUN) and creatinine were elevated more than three times of normal range.
- Presence of alcohol abuse/dependence or illicit drug abuse/dependence in previous 6 months before beginning of study.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University
Tainan, 70428
Tzu-Yun Wang, 886-6-2353535 ext. 5940, tzuyun0105@hotmail.com
About this study
Official title: The Potential Therapeutic Effects of add-on Low Dose Memantine to Improve Cognitive Deficits in Middle-to-old Aged Bipolar II Disorder Patients
The investigators hypothesized that add-on memantine (MM) 5 mg/day may reduce chronic inflammation, and subsequently improve neuro-progression process and cognitive function in middle-to-old aged bipolar II disorder (BP-II) patients. In current proposal, the investigators will conduct a randomized double-blind placebo-controlled study. The investigators will recruit 100-120 patients with BP-II who are older than 40 years old in three years, and allocate them to add-on MM or placebo plus standard valproic acid treatment in a 1: 1 ratio. The investigators will follow up the participants for 12 weeks and measure the severity of mood symptoms, neuropsychological tests and inflammatory markers to evaluate the therapeutic effects of add-on MM.
Read the detailed description
Emerging evidence showed that chronic inflammation and neuro-progression underlie bipolar disorder (BP). There were several neurobiological similarities between neuro-progression in BP and aging. Patients of BP also had many changes that were associated with early senescence. Meta-analysis showed that the association between dementia and BP were stronger than those with major depressive disorder, too. Therefore, some researchers proposed the theory of bipolar disorder as an illness of accelerated aging. However, BP is frequently under-recognized and misdiagnosed, especially bipolar II disorder (BP-II). Although the lifetime prevalence rate of BP-II ranges around 3-11%, many with BP-II were misdiagnosed as major depressive disorder and did not receive appropriate treatment. Therefore, neuro-progression may be found after decades of disease onset. The neuro-progression process, as accelerated aging process, may occur in the middle age period in BP-II patients, and contribute to the cognitive deficits, which were typically shown in old aged subjects with neurocognitive disorder. However, most of the past studies focused on bipolar I disorder (BP-I), there were few studies to investigate the early neuro-progression process in BP-II. Treatments for the cognitive deficits in middle-to-old aged BP-II patients were also lacked in literature.
Memantine (MM) has neuroprotective effects through the mechanisms of reducing neuroinflammation and increasing neurotrophic factors. The previous study showed that add-on low dose MM with mood stabilizers may attenuate inflammatory status and improve metabolic dysregulation in BP patients. Therefore, the investigators hypothesized that add-on MM 5 mg/day may reduce chronic inflammation, and subsequently improve neuro-progression process and cognitive function in middle-to-old aged BP-II patients. In current proposal, the investigators will conduct a randomized double-blind placebo-controlled study. The investigators will recruit 100-120 patients with BP-II who are older than 40 years old in three years, and allocate them to add-on MM or placebo plus standard valproic acid treatment in a 1: 1 ratio. The investigators will follow up the participants for 12 weeks and measure the severity of mood symptoms, neuropsychological tests and inflammatory markers to evaluate the therapeutic effects of add-on MM. The current proposal will provide the important data in whether add-on MM is able to improve the cognitive deficits due to neuro-progression in BP-II, and to prevent disease progression to a more severe form of neurocognitive disorder.
- Conditions
- Bipolar II Disorder
- Being tested
- Memantine or placebo
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Memantine or placeboDrug
BP-II patients who are older than 40 years old will be recruited, and allocate them to add-on memantine or placebo plus standard valproic acid treatment in a 1: 1 ratio. The participants will receive memantine 5mg/day or placebo treatment for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| memantine (MM) | Experimental | The participants will receive memantine 5mg (1 capsule) per day for 12 weeks. Receives: Drug: Memantine or placebo |
| Placebo | Placebo comparator | The participants will receive one capsule of placebo per day for 12 weeks. Receives: Drug: Memantine or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory function
The participants will receive the exam of Wechsler Memory Scale-III (WMS-III) at baseline and at the endpoint (after receiving memantine or placebo treatment for 12 weeks). WMS-III composite scores were calculated for the eight standardized primary indices: Auditory Immediate (AIM, range from 50-156), Visual Immediate (VIM, range from 47-162 ), Immediate Memory (IM, range from 40-164 ), Auditory Delayed (ADM, range from 46-162), Visual Delayed (VDM, range from 43-156), Auditory Recognition Delayed (ARDM, range from 55-145), General Memory (GM, range from 40-168), and Working Memory (WM, range from 45-156 ). Higher scores indicate better performance.
Measured: 12 weeks
Secondary outcomes (4)
executive function
The participants will receive the exam of Wisconsin Card Sorting Test (WCST)at baseline and at the endpoint (after receiving memantine or placebo treatment for 12 weeks). Performance on the WCST was scored in terms of the total number of errors (TNE, range form 0-128), perseverative errors (PE, range from 0-118), conceptual level responses (CLRs, range from 0-100%), number of categories completed (NCC, range form 0-12), and trials to complete the first category (TCC, range from 0-128). Higher scores indicate worse performance in TNE, PE, and TCC. Higher scores indicate better performance in CLRs and NCC.
Measured: 12 weeks
Attention
The participants will receive the exam of Continuous performance tests at baseline and at the endpoint (after receiving memantine or placebo treatment for 12 weeks). The CPT produces a standard set of performance measures that include the number of errors of omission and errors of commission. (1) Errors of omission occur when the participant fails to respond to the target stimulus. The omission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance. (2) Errors of commission occur when the participant responds to a non-target (X) stimulus. The commission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance.
Measured: 12 weeks
Processing speed
The participants will receive the exam of Trial-Making Test at baseline and at the endpoint (after receiving memantine or placebo treatment for 12 weeks). Higher score indicate worse performance.
Measured: 12 weeks
Inflammatory status
The plasma levels of cytokines and neurotrophic factors, tumor necrosis factor α (TNF-α[pg/mL]), C-reactive protein (CRP[pg/mL]), transforming growth factor β1 (TGF-β1 [pg/mL]), interleukin 6( IL-6[pg/mL]), interleukin 8(IL-8[pg/mL]), interleukin 1β (IL-1β[pg/mL]), and brain-derived neurotrophic factor(BDNF[pg/mL]), will be measured in participants at baseline and at the endpoint (after receiving memantine or placebo treatment for 12 weeks).
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2019
- Study start1 Aug 2019
- Primary completion31 Jul 2021 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar II DisorderStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Responsible party
- Principal investigator, Tzu-Yun Wang, National Cheng-Kung University Hospital
- Investigators
- Tzu-Yun Wang, Principal investigator, College of Medicine, National Cheng Kung University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04035798
- Sponsor's protocol ID
- A-BR-107-095
- Status last verified
- Mar 2021
- First submitted
- 1 Jul 2019
- Last updated
- 9 Mar 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Potential Therapeutic Effects of add-on Low Dose Memantine to Improve Cognitive Deficits in Middle-to-old Aged Bipolar II Disorder Patients
- ClinicalTrials.gov ID
- NCT04035798
- Acronym / sponsor ID
- A-BR-107-095
- Conditions
- Bipolar II Disorder
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 31 Jul 2021 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 29 Jul 2019 (actual)
- 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 investigators hypothesized that add-on memantine (MM) 5 mg/day may reduce chronic inflammation, and subsequently improve neuro-progression process and cognitive function in middle-to-old aged bipolar II disorder (BP-II) patients. In current proposal, the investigators will conduct a randomized double-blind placebo-controlled study. The investigators will recruit 100-120 patients with BP-II who are older than 40 years old in three years, and allocate them to add-on MM or placebo plus standard valproic acid treatment in a 1: 1 ratio. The investigators will follow up the participants for 12 weeks and measure the severity of mood symptoms, neuropsychological tests and inflammatory markers to evaluate the therapeutic effects of add-on MM.
Detailed description
Emerging evidence showed that chronic inflammation and neuro-progression underlie bipolar disorder (BP). There were several neurobiological similarities between neuro-progression in BP and aging. Patients of BP also had many changes that were associated with early senescence. Meta-analysis showed that the association between dementia and BP were stronger than those with major depressive disorder, too. Therefore, some researchers proposed the theory of bipolar disorder as an illness of accelerated aging. However, BP is frequently under-recognized and misdiagnosed, especially bipolar II disorder (BP-II). Although the lifetime prevalence rate of BP-II ranges around 3-11%, many with BP-II were misdiagnosed as major depressive disorder and did not receive appropriate treatment. Therefore, neuro-progression may be found after decades of disease onset. The neuro-progression process, as accelerated aging process, may occur in the middle age period in BP-II patients, and contribute to the cognitive deficits, which were typically shown in old aged subjects with neurocognitive disorder. However, most of the past studies focused on bipolar I disorder (BP-I), there were few studies to investigate the early neuro-progression process in BP-II. Treatments for the cognitive deficits in middle-to-old aged BP-II patients were also lacked in literature.
Memantine (MM) has neuroprotective effects through the mechanisms of reducing neuroinflammation and increasing neurotrophic factors. The previous study showed that add-on low dose MM with mood stabilizers may attenuate inflammatory status and improve metabolic dysregulation in BP patients. Therefore, the investigators hypothesized that add-on MM 5 mg/day may reduce chronic inflammation, and subsequently improve neuro-progression process and cognitive function in middle-to-old aged BP-II patients. In current proposal, the investigators will conduct a randomized double-blind placebo-controlled study. The investigators will recruit 100-120 patients with BP-II who are older than 40 years old in three years, and allocate them to add-on MM or placebo plus standard valproic acid treatment in a 1: 1 ratio. The investigators will follow up the participants for 12 weeks and measure the severity of mood symptoms, neuropsychological tests and inflammatory markers to evaluate the therapeutic effects of add-on MM. The current proposal will provide the important data in whether add-on MM is able to improve the cognitive deficits due to neuro-progression in BP-II, and to prevent disease progression to a more severe form of neurocognitive disorder.
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 |
|---|---|---|
| memantine (MM) | Experimental | Drug: Memantine or placeboThe participants will receive memantine 5mg (1 capsule) per day for 12 weeks. |
| Placebo | Placebo comparator | Drug: Memantine or placeboThe participants will receive one capsule of placebo per day for 12 weeks. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Signed informed consent by patient or legal representative.
- Male or female patient aged ≧40 years.
- A diagnosis of bipolar II disorder according to Diagnostic and Statistical Manual of Mental Disorders criteria made by a specialist in psychiatry.
- Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.
Key exclusion criteria (9 listed)
- Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.
- Females who are pregnant or lactation.
- Comorbid with substance-related disorders, borderline personality disorder, schizophrenia, mental retardation, dementia or other major psychiatric disorders. But comorbid with anxiety disorder or tobacco use disorder is not an exclusion criteria.
- Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.
- History of allergy or intolerable side effects of valproic acid, memantine, risperidone, fluoxetine, lorazepam.
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 |
|---|---|---|
| Memantine or placeboBP-II patients who are older than 40 years old will be recruited, and allocate them to add-on memantine or placebo plus standard valproic acid treatment in a 1: 1 ratio. The participants will receive memantine 5mg/day or placebo treatment for 12 weeks. | Drug | Placebo, memantine (MM) |
Primary outcome
Memory function
Time frame: 12 weeks
The participants will receive the exam of Wechsler Memory Scale-III (WMS-III) at baseline and at the endpoint (after receiving memantine or placebo treatment for 12 weeks). WMS-III composite scores were calculated for the eight standardized primary indices: Auditory Immediate (AIM, range from 50-156), Visual Immediate (VIM, range from 47-162 ), Immediate Memory (IM, range from 40-164 ), Auditory Delayed (ADM, range from 46-162), Visual Delayed (VDM, range from 43-156), Auditory Recognition Delayed (ARDM, range from 55-145), General Memory (GM, range from 40-168), and Working Memory (WM, range from 45-156 ). Higher scores indicate better performance.
4 secondary outcomes
executive function
Time frame: 12 weeks
Attention
Time frame: 12 weeks
Processing speed
Time frame: 12 weeks
Inflammatory status
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- 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.
Tzu-Yun Wang principal investigator
College of Medicine, National Cheng Kung University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study of Bipolar II Disorder, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
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 4 inclusion and 9 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 9 Mar 2021. 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 Taiwan. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Tzu-Yun Wang (886-6-2353535 ext. 6739, tzuyun0105@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Memory function (time frame: 12 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 9 Mar 2021.