Phase 2 Trial of a Nicotinic Agonist in Schizophrenia

NCT ID: NCT00100165

Last Updated: 2020-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2007-07-31

Brief Summary

The study hypothesis is that 3-2,4 dimethoxybenzylidene anabaseine (DMXB-A), an orally administered nicotinic cholinergic agonist, will improve attention and other neuropsychological dysfunctions in schizophrenia, leading to improved psychosocial outcome.

Detailed Description

The objective of the trial is to determine if dosing 3-(2,4 dimethoxybenzylidene anabaseine) twice daily for 4 weeks will improve cognition and be safe. Secondary goals are to determine if these neurocognitive effects also have effects on neurobiological paradigms previously shown to be responsive to nicotinic receptor stimulation: suppression of P50 auditory evoked response, saccadic intrusions during smooth pursuit eye movements, and hemodynamic activity in the hippocampus during smooth pursuit eye movements as measured by functional magnetic resonance imaging. The purpose of these neurobiological measures is to assess whether the response to 3-(2,4 dimethoxybenzylidene anabaseine) is consistent with activation of nicotinic receptors. In addition, the investigators will assess clinical response using a battery of clinical assessment scales and assessments of daily living functions. The purpose of these assessments is to address the FDA requirement of a clinical effect beyond change in laboratory neuropsychological performance. This study and the subsequent two studies will also include assessments of the safety of 3-(2,4 dimethoxybenzylidene anabaseine) and related compounds.

The purpose of the trial is to lay the groundwork for Phase III investigation. If this trial finds that 3-(2,4 dimethoxybenzylidene anabaseine) has effects at a safe dose, without tachyphylaxis, then the investigators intend to proceed to a Phase III trial, where the clinical importance of this effect can be measured.

The trial will be a double blind trial with placebo control. The order of doses and placebo will be randomized.

The Phase 1 study was completed in January, 2005, with 12 non-smoking schizophrenics subjects. The subjects were concurrently treated with neuroleptics throughout the study. They received 3 treatments, each for 1 day, in a double-blind crossover design. The treatments were 3-(2,4 dimethoxybenzylidene anabaseine) (150 mg + 75 mg 2 hours later), 3-(2,4 dimethoxybenzylidene anabaseine)(75 mg + 37.5 mg 2 hours later), and placebo. A significant effect on neurocognition, as measured by the Repeatable Battery for Assessment of Neuropsychological Status, and on sensory gating, as measured by P50 auditory evoked potentials was observed. Subjects reported no significant symptoms. One subject's white blood cell count decreased from just above normal limits on placebo to just below normal levels on 3-(2,4 dimethoxybenzylidene anabaseine)(150 + 75 mg 2 hours later). He did not receive further exposure to drug and his white blood cell count returned to normal at the next testing, 2 days later.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

3-(2,4 dimethoxybenzylidene anabaseine) 150 mg

Patient receives 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg twice per day in a blinded capsule.

Group Type: EXPERIMENTAL

3-(2,4 dimethoxybenzylidene anabaseine) 150 mg

Intervention Type: DRUG

3-(2,4 dimethoxybenzylidene) 150 mg by mouth twice a day for 4 weeks

3-(2,4 dimethoxybenzylidene anabaseine)75 mg

Patient receives 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg twice per day in a blinded capsule.

Group Type: EXPERIMENTAL

3-(2,4 dimethoxybenzylidene anabaseine) 75 mg

Intervention Type: DRUG

3-(2,4 dimethoxybenzylidene) 75 mg by mouth twice a day for 4 weeks

placebo

Patient receives placebo twice per day in a blinded capsule.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo by mouth twice a day for 4 weeks

Interventions

Placebo

Placebo by mouth twice a day for 4 weeks

Intervention Type: DRUG

3-(2,4 dimethoxybenzylidene anabaseine) 150 mg

3-(2,4 dimethoxybenzylidene) 150 mg by mouth twice a day for 4 weeks

Intervention Type: DRUG

3-(2,4 dimethoxybenzylidene anabaseine) 75 mg

3-(2,4 dimethoxybenzylidene) 75 mg by mouth twice a day for 4 weeks

Intervention Type: DRUG

Other Intervention Names

inactive substance; GTS-21; GTS-21

Eligibility Criteria

Inclusion Criteria

• Schizophrenia
• Currently treated with neuroleptic drugs

Exclusion Criteria

• Treatment with clozapine;
• Head injury or neurological condition;
• Cardiovascular disease;
• Substance abuse or dependence, including nicotine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Freedman, MD

Role: PRINCIPAL_INVESTIGATOR

VA Eastern Colorado Health Care System, Denver, CO

Locations

VA Eastern Colorado Health Care System, Denver, CO

Denver, Colorado, United States

Countries

United States

References

Tregellas JR, Tanabe J, Rojas DC, Shatti S, Olincy A, Johnson L, Martin LF, Soti F, Kem WR, Leonard S, Freedman R. Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia. Biol Psychiatry. 2011 Jan 1;69(1):7-11. doi: 10.1016/j.biopsych.2010.07.004. Epub 2010 Aug 21.

Reference Type: DERIVED

PMID: 20728875 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 18381905 (View on PubMed)

Other Identifiers

VISN 19 MIRECC

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

08-0837

Identifier Type: -

Identifier Source: org_study_id