Galantamine and Memantine Combination for Cognitive Impairments in Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Cognitive Dysfunction; Psychotic Disorders
Intervention: Galantamine ER; Memantine XR
Intervention MeSH terms: Memantine; Galantamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Schizophrenia; Schizoaffective Disorder; Cognition; Cognitive Impairment; Galantamine; Memantine

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.
    

Eligibility criteria:

        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.