A Multicenter Study of NAP (AL-108) in Schizophrenia

NCT00505765 | Completed Phase 2 Results DMC

• 2 other identifiers: TURNS03HHSN 278200441003C
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 8

Brief Summary

The TURNS is a NIMH-funded contract for the evaluation of new compounds for the treatment of cognitive impairments in schizophrenia (HHSN 27820044 1003C; P.I.: Steve Marder, M.D.). Despite advances in the safety, tolerability, and effectiveness of antipsychotic medications for the treatment of schizophrenia, many patients continue to be plagued by impairments in social and work functioning. Persons with schizophrenia commonly show deficits in a number of areas of cognition that include impairments in attention, memory, and executive functioning (the ability and organize one's behavior). Importantly, a large body of literature now shows a link between cognition and community functioning in schizophrenia. It is believed that treatments that improve cognitive deficits may lead to improvements in work and social functioning. One approach to improve the community functioning of patients with schizophrenia is to develop new agents that treat the cognitive deficits of the illness. A promising agent is called AL-108. This drug is administered as a nasal spray. Studies in animals suggest that this drug may protect neurons and may improve cognition in schizophrenia. The current study is a twelve-week multicenter, double-blind, randomized clinical trial of two doses of AL-108 (5 and 30 mg/day intranasally) versus placebo in the treatment of persistent cognitive dysfunction in schizophrenia. The study medication will be added to patients' current atypical antipsychotic medication or to their current injectable first-generation antipsychotic medication. The primary outcome measure will consist of the composite score of the MATRICS neuropsychological battery. Secondary outcome measures will include scores on symptoms, functional outcome, and safety measures. Sixty clinically stable patients with schizophrenia, drawn from eight sites, will participate in the study. Twenty-five patients will be enrolled at UCLA.

Conditions

Schizophrenia

Keywords

Cognition; Schizophrenia

Outcome Measures

Primary Outcomes (2)

• Change in MATRICS Consensus Cognitive Battery Composite Score Change

  The MATRICS Consensus Cognitive Battery (MCCB) measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and \< 40 (below normal range).

  Baseline, week 6

• Change in MATRICS Consensus Cognitive Battery (MCCB)

  The MATRICS Consensus Cognitive Battery (MCCB) measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and \< 40 (below normal range).

  Baseline, 12 weeks

Secondary Outcomes (4)

• Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores

  Baseline, week 6

• Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores

  Baseline, 12 weeks

• Change in SCoRS Interviewer Global Rating

  Baseline, 6 weeks

• Change in SCoRS Interviewer Global Rating

  Baseline, 12 weeks

Study Arms (4)

AL-108, 30 mg/day

EXPERIMENTAL

AL-108, 30 mg/day- 3 sprays in each nostril, twice per day

Drug: AL-108

AL-108, 5 mg/day

EXPERIMENTAL

AL-108, 5 mg/day- one spray in each nostril once per day

Drug: AL-108

Placebo, 3 sprays BID

PLACEBO COMPARATOR

Placebo- 3 sprays in each nostril, twice per day

Drug: Placebo

Placebo, 1 Spray Daily

PLACEBO COMPARATOR

Placebo- one spray in each nostril, once per day

Drug: Placebo

Interventions

AL-108 DRUG

AL-108, 5 mg/day- one spray in each nostril once per day

AL-108, 5 mg/day

Placebo DRUG

Placebo- 3 sprays in each nostril, twice per day

Placebo, 3 sprays BID

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• DSM IV/DSM IV TR diagnosis of schizophrenia
• Capable of providing informed consent
• Males and Females
• Age: 18 and 60
• Caucasian or Non Caucasian
• Subjects will be treated with one of the following second generation antipsychotics: risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole for the previous two months, with no change in dose in the last month, and/or with injectable depot antipsychotics (fluphenazine or haloperidol decanoate) with no change in last 3 months.
• Subjects will meet the following symptom criteria:
• Average Brief Psychiatric Rating Scale (BPRS) item score \>3 (mild)
• Simpson-Angus Scale total score less than or equal to 6
• Calgary Depression Scale total score less than or equal to 10
• Subjects will meet the following cognitive performance criteria:
• Performance less than the maximum cutoff (in parentheses) for ONE of the following MCCB tests:
• Letter-number span (20);
• HVLT total (31); and
• CPT d-prime (3.47)

You may not qualify if:

• Current treatment with oral conventional antipsychotics (e.g. fluphenazine, haloperidol) or clozapine.
• Subjects with a DSM-IV diagnosis of alcohol or substance abuse (other than nicotine) within the last month or a DSM-IV diagnosis of alcohol or substance dependence (other than nicotine) within the last 6 months
• Subjects with a history of significant head injury/trauma, as defined by one or more of the following:
• Loss of consciousness (LOC) for more than 1 hour
• Recurring seizures resulting from the head injury
• Clear cognitive sequellae of the injury
• Cognitive rehabilitation following the injury
• Subjects with a clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder (e.g. unstable angina, decompensated congestive heart failure, CNS infection or history of HIV seropositivity), which would pose a risk to the patient if they were to participate in the study or that might confound the results of the study.
• Clinically significant abnormalities in physical examination, ECG, or laboratory assessments.
• Clinically significant renal disease.
• Women who are pregnant or of child-bearing potential, either not surgically-sterile nor using appropriate methods of birth control
• Women who are breast-feeding
• Prior participation in a clinical trial of investigational medication within 60 days.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• University of Maryland: collaborator
• Washington University School of Medicine: collaborator
• Massachusetts General Hospital: collaborator
• Nathan Kline Institute for Psychiatric Research: collaborator
• Columbia University: collaborator
• Duke University: collaborator
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (8)

UCLA

Los Angeles, California, 90073, United States

Location

Maryland Psychiatric Research Center

Catonsville, Maryland, 21228, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Harvard Medical School

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (26)

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  PMID: 28433500 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

davunetide

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Stephen R. Marder
• Organization: Semel Institute at UCLA

marder@ucla.edu

310-268-3647

Study Officials

• Daniel C Javitt, MD, PhD

  Nathan Kline Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2007
• First Posted: July 23, 2007
• Study Start: July 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: March 10, 2017
• Results First Posted: January 27, 2017

Record last verified: 2017-01

Locations

US (8)