SchizophreniaPhase 2NCT02234752
Galantamine and Memantine Combination for Cognitive Impairments in Schizophrenia
A Phase 2 study testing Galantamine ER and Memantine XR in people with Schizophrenia and Schizoaffective Disorder, run by Sheppard Pratt Health System at 1 site in United States.
Trial summary
Aim: To examine the efficacy of the combination of galantamine and memantine for the treatment of cognitive deficits in outpatients with schizophrenia. Hypothesis: A combination of galantamine and memantine will improve cognitive impairments in patients with schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Galantamine ER and Memantine XR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Jul 2016
- Phase
- Phase 2
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Be male or female aged 18 to 55 years (inclusive).
- Have a DSM-5 diagnosis of schizophrenia or schizoaffective disorder confirmed by medical records. Duration of illness must be ≥ 1year.
- Be clinically stable for at least two months (i.e., has no more than a "moderately severe" severity rating on the following BPRS items: hallucination, unusual thought content and conceptual disorganization.
- Have not had a psychiatric hospitalization in the two months prior to screening.
- Be taking any 1st generation antipsychotic prescribed in the absence of a concomitant anticholinergic or 2nd generation antipsychotic and minimal extrapyramidal symptoms
- Have a Simpson-Angus Score (SAS) < 6
Show all 13Show fewer
- Be on current medication regimen for at least six weeks before screening at stable dose and frequency for at least 30 days before screening.
- Be in good general health and expected to complete the clinical study as designed.
- Subjects of childbearing potential must agree to use two forms of non-hormonal contraception (dual contraception) consistently during the screening and treatment periods of the trial, and for 30 days after the final dose of the study medications.
- Females of child-bearing potential must have a negative urine pregnancy test at baseline. This may also be done at subsequent visits if subject reports possibility of pregnancy.
- Have a negative urine drug screen at screening. This may be repeated at the discretion of the primary investigator.
- Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
- Be capable of providing informed consent and have voluntarily provided informed consent.
Who cannot join
- Have an active, clinically significant unstable medical condition with 30 days prior to screening.
- Have dementia.
- Are pregnant, breastfeeding, or planning to become pregnant
- Are taking or thinking about taking oral contraceptives or an injectable contraceptive.
- Are taking benztropine at a dose greater than 2 mg daily.
- Have a history of Pervasive Development Disorder.
Show all 16Show fewer
- Have a history of significant head injury/trauma (defined by one of more of the following: loss of consciousness for more than one hour; recurring seizures resulting from the head injury; and/or clear cognitive sequelae of the injury requiring cognitive rehabilitation.)
- Have an allergy to anticholinesterase medications (galantamine, rivastigimine, donepezil) and memantine
- Have a DSM-5 diagnosis of alcohol and/or substance use disorder (other than caffeine and tobacco) within the last 6 months.
- Are taking a restricted medication: Amitriptyline, Doxepin, Imipramine, Flexeril, Clozapine, and/or cortisol (any oral, injectable, or topical steroid medication)
- Have a history of seizures excluding a childhood febrile seizure
- Have received ECT within the last three months prior to screening.
- Have participated in a clinical trial of any other psychotropic medication within last two months prior to screening.
- Have a "severe" or "extremely severe" severity rating on the BPRS items: hallucination or unusual thought content.
- Have more than a "moderate" severity rating on the BPRS item conceptual disorganization .
- Are currently taking 3 or more antipsychotic medications.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sheppard Pratt Health System
Baltimore, Maryland, 21204
About this study
Official title: A Proof-of Concept Trial of Galantamine and Memantine for Cognitive Impairments in Schizophrenia: Is the Combination Effective?
Aim: To examine the efficacy of the combination of galantamine and memantine for the treatment of cognitive deficits in outpatients with schizophrenia.
Hypothesis: A combination of galantamine and memantine will improve cognitive impairments in patients with schizophrenia.
This is an open-label study to evaluate whether a six week course of galantamine ER and memantine XR is effective in improving the cognitive performance of patients with schizophrenia or schizoaffective disorder. The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). The results of the MATRICS collaborative project recommended the need for standardized cognitive tests that better distinguish the different facets of cognitive dysfunction in schizophrenia. The MCCB will assess the following seven domains: attention/vigilance, reasoning and problem solving, processing speed, social cognition, verbal learning and memory, visual learning and memory, and working memory. The MCCB will be administered at baseline and at the end of the study. We will report total score and each domain score in the MCCB at baseline and six weeks.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Galantamine ER, Memantine XR
- Keywords
- Schizophrenia, Schizoaffective Disorder, Cognition, Cognitive Impairment, Galantamine, Memantine
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Galantamine ERDrug
Also called Razadyne, Razadyne ER, Formerly known as Reminyl
Memantine XRDrug
Also called Namenda
| Study group | Role | What they receive |
|---|---|---|
| Galantamine ER, Memantine XR | Experimental | Week 1, Galantamine ER 8 mg HS \& Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS \& Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS \& Memantine XR 21 mg HS Receives: Drug: Galantamine ER; Drug: Memantine XR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Level of Cognition
The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported.
Measured: Baseline and 6-Weeks
Secondary outcomes (7)
Free Tryptophan (TRP)
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.
Measured: Baseline and 6-Weeks
Kynurenic Acid (KYNA)
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.
Measured: Baseline and 6-Weeks
Kynurenine (KYN)
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.
Measured: Baseline and 6-Weeks
Picolinic Acid (PIC)
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.
Measured: Baseline and 6-Weeks
KYN/TRP
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
Measured: Baseline and 6-Weeks
KYNA/KYN
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
Measured: Baseline and 6-Weeks
PIC/KYN
The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
Measured: Baseline and 6-Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: Funding no longer available and PI no longer working at the institution
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 (3)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheppard Pratt Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maju Koola, Sheppard Pratt Health System
- Investigators
- Maju M. Koola, MD, Principal investigator, Sheppard Pratt Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02234752
- Sponsor's protocol ID
- SPHS IRB # 604148-4
- Status last verified
- Oct 2016
- First submitted
- 4 Sep 2014
- Last updated
- 9 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Koola MM, Buchanan RW, Pillai A, Aitchison KJ, Weinberger DR, Aaronson ST, Dickerson FB. Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia. Schizophr Res. 2014 Aug;157(1-3):84-9. doi: 10.1016/j.schres.2014.04.037. Epub 2014 May 28.
PubMed 24878431Koola MM. Kynurenine pathway and cognitive impairments in schizophrenia: Pharmacogenetics of galantamine and memantine. Schizophr Res Cogn. 2016 Jun;4:4-9. doi: 10.1016/j.scog.2016.02.001.
PubMed 27069875Koola MM, Sklar J, Davis W, Nikiforuk A, Meissen JK, Sawant-Basak A, Aaronson ST, Kozak R. Kynurenine pathway in schizophrenia: Galantamine-memantine combination for cognitive impairments. Schizophr Res. 2018 Mar;193:459-460. doi: 10.1016/j.schres.2017.07.005. Epub 2017 Jul 11. No abstract available.
PubMed 28705532
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of Concept Trial of Galantamine and Memantine for Cognitive Impairments in Schizophrenia: Is the Combination Effective?
- ClinicalTrials.gov ID
- NCT02234752
- Acronym / sponsor ID
- SPHS IRB # 604148-4
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- Schizophrenia, Schizoaffective Disorder, Cognition, Cognitive Impairment, Galantamine, Memantine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding no longer available and PI no longer working at the institution
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Sheppard Pratt Health SystemUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 9 Sep 2014 (estimated)
- Results
- Posted 9 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim: To examine the efficacy of the combination of galantamine and memantine for the treatment of cognitive deficits in outpatients with schizophrenia.
Hypothesis: A combination of galantamine and memantine will improve cognitive impairments in patients with schizophrenia.
This is an open-label study to evaluate whether a six week course of galantamine ER and memantine XR is effective in improving the cognitive performance of patients with schizophrenia or schizoaffective disorder. The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). The results of the MATRICS collaborative project recommended the need for standardized cognitive tests that better distinguish the different facets of cognitive dysfunction in schizophrenia. The MCCB will assess the following seven domains: attention/vigilance, reasoning and problem solving, processing speed, social cognition, verbal learning and memory, visual learning and memory, and working memory. The MCCB will be administered at baseline and at the end of the study. We will report total score and each domain score in the MCCB at baseline and six weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Galantamine ER, Memantine XR | Experimental | Drug: Galantamine ER, Drug: Memantine XRWeek 1, Galantamine ER 8 mg HS \& Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS \& Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS \& Memantine XR 21 mg HS |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Be male or female aged 18 to 55 years (inclusive).
- Have a DSM-5 diagnosis of schizophrenia or schizoaffective disorder confirmed by medical records. Duration of illness must be ≥ 1year.
- Be clinically stable for at least two months (i.e., has no more than a "moderately severe" severity rating on the following BPRS items: hallucination, unusual thought content and conceptual disorganization.
- Have not had a psychiatric hospitalization in the two months prior to screening.
- Be taking any 1st generation antipsychotic prescribed in the absence of a concomitant anticholinergic or 2nd generation antipsychotic and minimal extrapyramidal symptoms
Key exclusion criteria (16 listed)
- Have an active, clinically significant unstable medical condition with 30 days prior to screening.
- Have dementia.
- Are pregnant, breastfeeding, or planning to become pregnant
- Are taking or thinking about taking oral contraceptives or an injectable contraceptive.
- Are taking benztropine at a dose greater than 2 mg daily.
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 |
|---|---|---|
| Galantamine ERAlso: Razadyne, Razadyne ER, Formerly known as Reminyl | Drug | Galantamine ER, Memantine XR |
| Memantine XRAlso: Namenda | Drug | Galantamine ER, Memantine XR |
Primary outcome
Change in Level of Cognition
Time frame: Baseline and 6-Weeks
The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported.
7 secondary outcomes
Free Tryptophan (TRP)
Time frame: Baseline and 6-Weeks
Kynurenic Acid (KYNA)
Time frame: Baseline and 6-Weeks
Kynurenine (KYN)
Time frame: Baseline and 6-Weeks
Picolinic Acid (PIC)
Time frame: Baseline and 6-Weeks
KYN/TRP
Time frame: Baseline and 6-Weeks
KYNA/KYN
Time frame: Baseline and 6-Weeks
PIC/KYN
Time frame: Baseline and 6-Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24878431Koola MM, Buchanan RW, Pillai A, Aitchison KJ, Weinberger DR, Aaronson ST, Dickerson FB. Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia. Schizophr Res. 2014 Aug;157(1-3):84-9. doi: 10.1016/j.schres.2014.04.037. Epub 2014 May 28.
- Background: PubMed 27069875Koola MM. Kynurenine pathway and cognitive impairments in schizophrenia: Pharmacogenetics of galantamine and memantine. Schizophr Res Cogn. 2016 Jun;4:4-9. doi: 10.1016/j.scog.2016.02.001.
- Results publication: PubMed 28705532Koola MM, Sklar J, Davis W, Nikiforuk A, Meissen JK, Sawant-Basak A, Aaronson ST, Kozak R. Kynurenine pathway in schizophrenia: Galantamine-memantine combination for cognitive impairments. Schizophr Res. 2018 Mar;193:459-460. doi: 10.1016/j.schres.2017.07.005. Epub 2017 Jul 11. No abstract available.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
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.
Maju M. Koola, MD principal investigator
Sheppard Pratt Health System
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 Galantamine ER and Memantine XR in people with Schizophrenia and Schizoaffective Disorder, run by Sheppard Pratt Health System 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 13 inclusion and 16 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: stopped early, as of the sponsor's last update on 9 Nov 2017. 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 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?
Yes. Results are posted in the registry (first posted 9 Nov 2017). 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?
Change in Level of Cognition (time frame: Baseline and 6-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 NCT02234752, which also lists 3 linked publications.
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 Nov 2017.