Galantamine and Memantine Combination for Cognitive Impairments in Schizophrenia

A Proof-of Concept Trial of Galantamine and Memantine for Cognitive Impairments in Schizophrenia: Is the Combination Effective?

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02234752

Enrollment

Registered

2014-09-09

Start date

2014-09-30

Completion date

2016-07-31

Last updated

2017-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizoaffective Disorder, Schizophrenia

Keywords

Schizophrenia, Schizoaffective Disorder, Cognition, Cognitive Impairment, Galantamine, Memantine

Brief 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. 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.

Interventions

DRUGGalantamine ER

DRUGMemantine XR

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

* 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 * 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.

Exclusion criteria

* 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. * 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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Level of Cognition	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.

Secondary

Measure	Time frame	Description
Kynurenic Acid (KYNA)	Baseline and 6-Weeks	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.
Kynurenine (KYN)	Baseline and 6-Weeks	The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.
Picolinic Acid (PIC)	Baseline and 6-Weeks	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.
Free Tryptophan (TRP)	Baseline and 6-Weeks	The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.
KYNA/KYN	Baseline and 6-Weeks	The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
PIC/KYN	Baseline and 6-Weeks	The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
KYN/TRP	Baseline and 6-Weeks	The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Galantamine ER, Memantine XR 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 Galantamine ER Memantine XR	3
Total	3

Baseline characteristics

Characteristic	Galantamine ER, Memantine XR
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment United States	3 Participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 3
other Total, other adverse events	1 / 3
serious Total, serious adverse events	0 / 3

Outcome results

Primary

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.

Time frame: Baseline and 6-Weeks