Huperzine for Cognitive and Functional Impairment in Schizophrenia

Huperzine is a natural plant product with procognitive properties in patients with Alzheimer's disease. Cognitive difficulties hamper functioning in schizophrenia as well. The present study will investigate whether huperzine improves cognition and functioning in patients with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: placebo; Drug: huperzine 0.2 mg BID; Drug: huperzine 0.4 mg BID; Drug: huperzine 0.8 mg BID

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Psychiatric diagnosis of schizophrenia according to SCID-IV.
2. Currently treated with an antipsychotic medication.
3. Has tolerated current antipsychotic treatment adequately.
4. Has received an adequate trial of antipsychotic (a least 3 months of at least 300 mg/d CPZ equivalent).
5. Has been receiving current psychotropic medication (s) for at least 8 weeks.
6. Has been receiving current doses of psychotropic medication (s) for at least 4 weeks.
7. Has been clinically stable for at least 12 weeks.
8. No more than moderate severity (4 on the 1-7 scale) on any PANSS positive item.
9. No more than 15 on the total of PANSS negative symptom items.
10. Simpson-Angus Scale total score <7.
11. Calgary Depression Scale for Schizophrenia total score <11.
12. Submaximal performance on at least one of the following MATRICS components (letter-number span <20 OR HVLT total <31 OR CPT d-prime < 3.47).
13. Score > 1 SD below age-, gender-, and education-adjusted normal control mean on MATRICS composite
14. Good general health with no additional diseases expected to interfere with the studies.
15. Fluent in English.
16. Age 18-55.
17. Adequate visual and auditory acuity to allow neuropsychological testing.
18. Able to ingest oral medication.
19. Not pregnant or lactating (women of childbearing potential must use a medically accepted method of birth control).
20. Onset of schizophrenia prior to age 45.
21. Available informant knowledgeable about subject's current functioning.
22. Informed consent obtained from the subject prior to entry into the study.

Exclusion Criteria:

1. Poor reading skills (raw score on MATRICS Wechsler Test of Adult Reading < 6).
2. History of systemic cancer within 5 years.
3. Use of any investigational drugs within 30 days prior to the screening visit.
4. Use of cholinesterase inhibitors (galantamine, rivastigmine, donepezil, or tacrine) within 4 weeks of screening.
5. Any clinically significant laboratory test abnormality on screening tests (hematology, chemistry, urinalysis, EKG). Clinically significant LFT elevations will be defined as >2x the upper limit of normal.
6. Any significant neurologic disease including Alzheimer's disease, parkinson's disease, stroke, huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history of head injury with loss of consciousness for greater than one day within the past 5 years, or with residual deficits.
7. Use of antihypertensive agents with frequent CNS side effects (e.g. clonidine, propranolol) within 4 weeks prior to the screening visit.
8. Use of medications known to alter drug absorption or metabolism (e.g. probenecid, cimetidine, anti-fungal agents, erythromycin, rifampin, and anticonvulsants) within 4 weeks prior to the screening visit.
9. History of peptic ulcer disease within 2 years.
10. History of myocardial infarction, significant cardiovascular disease, or congestive heart failure within 6 months, history of hepatic or renal insufficiency, insulin-requiring diabetes or uncontrolled diabetes mellitus.
11. Clinically significant cardiac arrhythmia, resting pulse less than 50.
12. Present use or use in the 4 weeks prior to screening of anti-parkinsonian or anticholinergic medications (e.g. Sinemet, amantadine, bromocriptine, pergolide, selegiline, atropine, scopolamine, benztropine, trihexyphenidyl, hydroxyzine, diphenhydramine).
13. Use of narcotic analgesics within 4 weeks prior to the screening visit.
14. History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria).
15. Receiving CYP 1A2 inhibitors such as certain SSRIs (all excluded in #4) cimetidine, methoxsalen, quinolones, furafylline, or moclobemide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: placebo; matching pill placebo
EXPERIMENTAL: huperzine 0.2 mg BID	Drug: huperzine 0.2 mg BID; huperzine rising doses up to 0.2 mg BID
EXPERIMENTAL: huperzine 0.4 mg BID	Drug: huperzine 0.4 mg BID; huperzine rising doses up to 0.4 mg BID
EXPERIMENTAL: huperzine 0.8 mg BID	Drug: huperzine 0.8 mg BID; huperzine rising doses up to 0.8 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MATRICS battery	26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
UPSA	26 weeks

Collaborators and Investigators

• Sponsor: Biomedisyn Corporation
• Collaborators: Yale University
• Investigators: Principal Investigator: Scott W Woods, MD, Biomedisyn Corporation

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): December 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: August 10, 2009
• First Submitted That Met QC Criteria: August 21, 2009
• First Posted (ESTIMATE): August 24, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 1, 2013
• Last Update Submitted That Met QC Criteria: February 28, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: cognition; schizophrenia; functioning
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Huperzine A
• Other Study ID Numbers: Biomedisyn 200901; 3R41MH083436-01A1S1 (NIH)