Clinical trial NCT01400477: Nicotinic Receptors and Schizophrenia
Official title: Nicotinic Receptors and Schizophrenia: Phase II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: Drug Trial
Smoking
Smoking Cessation
Cognition
Mental Focus
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2011-07-22
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random allocation to a treatment and placebo group.
Primary purpose: TREATMENT

Brief summary: The investigators hypothesize that sustained-release DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) will provide clinical improvement in cognition in patients with schizophrenia who are smokers and who are non-smokers. The study drug may also maintain abstinence from cigarette smoking and improve other symptoms in patients with schizophrenia.

Detailed description: Patients with schizophrenia will be screened then enrolled for one week placebo trial in addition to their existing antipsychotic medication. If pill compliance is greater than 80%, then they will receive baseline clinical, cognitive, and brain imaging and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram. Then patients will receive in a randomized double blind trial either DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) or placebo comparator in addition to their existing antipsychotic medication. After one month patients will receive repeat clinical, cognitive, and brain imaging testing and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram.

Eligibility criteria: Inclusion Criteria:

* Subjects will be selected to be 18 to 65 years old and in good general health.
* Subjects who fulfill Diagnostic and Statistical Manual -IV-Text Revision (DSM-IV-TR) criteria for schizophrenia or schizoaffective disorder.
* Smokers will smoke at least 20 cigarettes per day.
* Non-smokers will also be enrolled.
* Subjects will have normal:

  * vital signs,
  * hematology,
  * serum chemistries,
  * EKG, and
  * urinalysis with a negative drug screen before entry into the study.
* Subjects will be fluent in English.
* Smoking subjects will be interested in stopping smoking in the near future and not interested in nicotine replacement therapy.

Exclusion Criteria:

* Subjects with histories of:

  * neurological illness,
  * liver disease,
  * severe hypertension (cut-off blood pressure 160/100) or
  * cardiac disease, or
  * renal failure (cut-off creatinine above 1.4).
* Subjects who currently meet DSM-IV-TR criteria for substance dependence other than nicotine, cannabis, or alcohol will be excluded.
* Women who are capable of pregnancy and not on acceptable forms of birth control will be excluded.
* Subjects being treated with Clozapine will be excluded.

Primary outcomes:
measure: Neurocognitive Efficacy
timeFrame: 4 weeks
Secondary outcomes:
measure: Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: UColorado Denver
state: Colorado
city: Aurora
country: United States
facility: University of Colorado-Anschutz Medical Campus, Department of Psychiatry
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Robert Freedman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R. Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. 2006 Jun;63(6):630-8. doi: 10.1001/archpsyc.63.6.630.
citation: Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, Allensworth D, Guzman-Bonilla A, Clement B, Ball MP, Kutnick J, Pender V, Martin LF, Stevens KE, Wagner BD, Zerbe GO, Soti F, Kem WR. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry. 2008 Aug;165(8):1040-7. doi: 10.1176/appi.ajp.2008.07071135. Epub 2008 Apr 1.
citation: Kem WR, Olincy A, Johnson L, Harris J, Wagner BD, Buchanan RW, Christians U, Freedman R. Pharmacokinetic Limitations on Effects of an Alpha7-Nicotinic Receptor Agonist in Schizophrenia: Randomized Trial with an Extended-Release Formulation. Neuropsychopharmacology. 2018 Feb;43(3):583-589. doi: 10.1038/npp.2017.182. Epub 2017 Aug 21.