SchizophreniaPhase 2DMXB-ANCT00100165
Phase 2 Trial of a Nicotinic Agonist in Schizophrenia
A Phase 2 study testing 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg and 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg in people with Schizophrenia, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg and 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Jul 2007
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Schizophrenia
- Currently treated with neuroleptic drugs
Who cannot join
- Treatment with clozapine;
- Head injury or neurological condition;
- Cardiovascular disease;
- Substance abuse or dependence, including nicotine
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Eastern Colorado Health Care System, Denver, CO
Denver, Colorado, 80220
About this study
Official title: Phase 2 Trial of the Nicotinic Agonist 3-(2,4 Dimethoxybenzylidene Anabaseine) in Schizophrenia
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.
Read the 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
- Being tested
- Placebo, 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg, 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg
- Keywords
- Schizophrenia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called inactive substance
Placebo by mouth twice a day for 4 weeks
3-(2,4 dimethoxybenzylidene anabaseine) 150 mgDrug
Also called GTS-21
3-(2,4 dimethoxybenzylidene) 150 mg by mouth twice a day for 4 weeks
3-(2,4 dimethoxybenzylidene anabaseine) 75 mgDrug
Also called GTS-21
3-(2,4 dimethoxybenzylidene) 75 mg by mouth twice a day for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg | Experimental | Patient receives 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg twice per day in a blinded capsule. Receives: Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg |
| 3-(2,4 dimethoxybenzylidene anabaseine)75 mg | Experimental | Patient receives 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg twice per day in a blinded capsule. Receives: Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg |
| placebo | Placebo comparator | Patient receives placebo twice per day in a blinded capsule. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive Performance
The measurement of neurocognitive performance on 6 domains, speed of processing, attention/vigilance, working memory, verbal learning, visual learning and reasoning/problem solving. Each domain is compared to a normative sample of schizophrenia subjects and the performance is determined and compared by a T-Test to the subjects baseline performance to determine the effect of drug or placebo. The scale is the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia Neurocognitive Consensus Combined Battery, range 0-100. A higher score indicates better performance.
Measured: 1 month
Secondary outcomes (1)
Scale for the Assessment of Negative Symptoms (SANS)
The Scale for the Assessment of Negative Symptoms measures the measure negative symptoms in schizophrenia by measuring the domains of anhedonia, alogia, avolition and anhedonia in schizophrenia on a scale from 1 to 20 that sums the global scores of all 4 domains, each of which are rated on a scale of 1-5. Higher scores indicate greater severity of negative symptoms
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2004 (estimated)
- Study startJan 2005
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- VA Office of Research and Development
- Responsible party
- Sponsor
- Investigators
- Robert Freedman, MD, Principal investigator, VA Eastern Colorado Health Care System, Denver, CO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00100165
- Sponsor's protocol ID
- 08-0837
- Other IDs
- VISN 19 MIRECC
- Acronym
- DMXB-A
- Status last verified
- Jan 2020
- First submitted
- 23 Dec 2004
- Last updated
- 29 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 20728875Freedman 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.
PubMed 18381905
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of the Nicotinic Agonist 3-(2,4 Dimethoxybenzylidene Anabaseine) in Schizophrenia
- ClinicalTrials.gov ID
- NCT00100165
- Acronym / sponsor ID
- DMXB-A / 08-0837
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- VA Office of Research and Development
- Study start
- Jan 2005
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 24 Dec 2004 (estimated)
- Results
- Posted 29 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg | Experimental | Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 150 mgPatient receives 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg twice per day in a blinded capsule. |
| 3-(2,4 dimethoxybenzylidene anabaseine)75 mg | Experimental | Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 75 mgPatient receives 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg twice per day in a blinded capsule. |
| placebo | Placebo comparator | Drug: PlaceboPatient receives placebo twice per day in a blinded capsule. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Schizophrenia
- Currently treated with neuroleptic drugs
Key exclusion criteria (4 listed)
- Treatment with clozapine;
- Head injury or neurological condition;
- Cardiovascular disease;
- Substance abuse or dependence, including nicotine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: inactive substancePlacebo by mouth twice a day for 4 weeks | Drug | placebo |
| 3-(2,4 dimethoxybenzylidene anabaseine) 150 mgAlso: GTS-213-(2,4 dimethoxybenzylidene) 150 mg by mouth twice a day for 4 weeks | Drug | 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg |
| 3-(2,4 dimethoxybenzylidene anabaseine) 75 mgAlso: GTS-213-(2,4 dimethoxybenzylidene) 75 mg by mouth twice a day for 4 weeks | Drug | 3-(2,4 dimethoxybenzylidene anabaseine)75 mg |
Primary outcome
Neurocognitive Performance
Time frame: 1 month
The measurement of neurocognitive performance on 6 domains, speed of processing, attention/vigilance, working memory, verbal learning, visual learning and reasoning/problem solving. Each domain is compared to a normative sample of schizophrenia subjects and the performance is determined and compared by a T-Test to the subjects baseline performance to determine the effect of drug or placebo. The scale is the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia Neurocognitive Consensus Combined Battery, range 0-100. A higher score indicates better performance.
1 secondary outcome
Scale for the Assessment of Negative Symptoms (SANS)
Time frame: 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20728875Tregellas 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.
- Derived from this study: PubMed 18381905Freedman 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Freedman, MD principal investigator
VA Eastern Colorado Health Care System, Denver, CO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg and 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg in people with Schizophrenia, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurocognitive Performance (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00100165, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2020.