Galantamine and Memantine Combination for Cognitive Impairments in Schizophrenia

November 6, 2017 updated by: Maju Koola, Sheppard Pratt Health System

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Sheppard Pratt Health System

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

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: Galantamine ER
Other Names:
  • Razadyne
  • Razadyne ER
  • Formerly known as Reminyl
Drug: Memantine XR
Other Names:
  • Namenda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and 6-Weeks

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

Sheppard Pratt Health System

Investigators

  • Principal Investigator: Maju M. Koola, MD, Sheppard Pratt Health System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2014

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

September 4, 2014

First Submitted That Met QC Criteria

September 5, 2014

First Posted (Estimate)

September 9, 2014

Study Record Updates

Last Update Posted (Actual)

November 9, 2017

Last Update Submitted That Met QC Criteria

November 6, 2017

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPHS IRB # 604148-4

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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