Primary outcomeMean· Baseline, week 6
Change in MATRICS Consensus Cognitive Battery Composite Score Change
| Group | Value (units on a scale) | Spread |
|---|---|---|
| AL-108, 30 mg/Day | 1.3 | 4.6 |
| AL-108, 5 mg/Day | 2.3 | 4.6 |
| Placebo | -0.2 | 5.6 |
Trial · Interventional
CompletedPhase 2Results postedRegistry dataA Multicenter Study of NAP (AL-108) in Schizophrenia
Short name AL-108
Overview
- Status
- Completed
- Phase
- Phase 2
- Enrollment
- 63 participants (actual)
- Sponsor
- University of California, Los Angeles · Other
- Design
- Randomized · Double masking
- Countries
1 country
United States
- Start
- Jul 2007
- Primary completion
- Apr 2009
- Completion
- Apr 2009
- First posted
- 23 Jul 2007 (estimated)
- Last update posted
- 10 Mar 2017
- Conditions
- Schizophrenia
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2007200820092010
- Ph 2
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- AL-108Drug
- AL-108Drug
- PlaceboDrug
- PlaceboDrug
Arms4
Experimental
AL-108, 30 mg/day
AL-108, 30 mg/day- 3 sprays in each nostril, twice per day
Experimental
AL-108, 5 mg/day
AL-108, 5 mg/day- one spray in each nostril once per day
Placebo comparator
Placebo, 3 sprays BID
Placebo- 3 sprays in each nostril, twice per day
Placebo comparator
Placebo, 1 Spray Daily
Placebo- one spray in each nostril, once per day
Primary outcomes2
Outcomes the sponsor listed as primary.
Change in MATRICS Consensus Cognitive Battery Composite Score Change
Time frame · Baseline, week 6
Registry description
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).
Change in MATRICS Consensus Cognitive Battery (MCCB)
Time frame · Baseline, 12 weeks
Registry description
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).
Secondary outcomes(4)
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
Time frame · Baseline, week 6
Registry description
UPSA includes 5 skill areas (subscales) with scores that each range from 0-20. The UPSA yields an overall total score which is the sum of the five subscales and ranges from 0-100. Higher scores are associated with more independent living.
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
Time frame · Baseline, 12 weeks
Registry description
UPSA includes 5 skill areas (subscales) with scores that each range from 0-20. The UPSA yields an overall total score which is the sum of the five subscales and ranges from 0-100. Higher scores are associated with more independent living.
Change in SCoRS Interviewer Global Rating
Time frame · Baseline, 6 weeks
Registry description
Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity by completing a 20-question rating scale via interviews with the subject and an informant, focusing on cognitive impairment and its impact on daily functioning. After the interview, the interviewer rated subject's overall difficulty on a Global Scale of 1-10. Higher scores indicate greater cognitive impairment.
Change in SCoRS Interviewer Global Rating
Time frame · Baseline, 12 weeks
Registry description
Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity by completing a 20-question rating scale via interviews with the subject and an informant, focusing on cognitive impairment and its impact on daily functioning. After the interview, the interviewer rated subject's overall difficulty on a Global Scale of 1-10. Higher scores indicate greater cognitive impairment.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Primary outcomeMean· Baseline, 12 weeks
Change in MATRICS Consensus Cognitive Battery (MCCB)
| Group | Value (units on a scale) | Spread |
|---|---|---|
| AL-108, 30 mg/Day | 3.9 | 4.6 |
| AL-108, 5 mg/Day | 4.6 | 7.2 |
| Placebo | 3.2 | 4.9 |
Secondary and other outcome results(4)
Secondary outcomeMean· Baseline, week 6
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
| Group | Value (units on a scale) | Spread |
|---|---|---|
| AL-108, 30 mg/Day | 2.9 | 7.6 |
| AL-108, 5 mg/Day | 7.2 | 7.3 |
| Placebo | -0.9 | 9.0 |
Secondary outcomeMean· Baseline, 12 weeks
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
| Group | Value (units on a scale) | Spread |
|---|---|---|
| AL-108, 30 mg/Day | 4.9 | 19 |
| AL-108, 5 mg/Day | 8.9 | 6.6 |
| Placebo | 0.3 | 8.5 |
Secondary outcomeMean· Baseline, 6 weeks
Change in SCoRS Interviewer Global Rating
| Group | Value (units on a scale) | Spread |
|---|---|---|
| AL-108, 30 mg/Day | 0.1 | 1.2 |
| AL-108, 5 mg/Day | -0.6 | 1.3 |
| Placebo | -0.1 | 1.0 |
Secondary outcomeMean· Baseline, 12 weeks
Change in SCoRS Interviewer Global Rating
| Group | Value (units on a scale) | Spread |
|---|---|---|
| AL-108, 30 mg/Day | -0.4 | 1.1 |
| AL-108, 5 mg/Day | -1.2 | 1.6 |
| Placebo | -0.3 | 1.5 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| AL-108, 30 mg/DayAL-108, 30 mg/day- 3 sprays in each nostril, twice per day | – | 1 / 21 | 4 / 21 |
| AL-108, 5 mg/DayAL-108, 5 mg/day- one spray in each nostril once per day | – | 0 / 20 | 9 / 20 |
| PlaceboPlacebo, low-dose: 1 puff administered in each nostril daily (QD) Placebo, high-dose: 3 puffs administered twice daily in each nostril (BID) Data were combined across placebo conditions for analysis | – | 0 / 22 | 2 / 22 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies4
Studies that cite this trial.
Studies with results
3 studies on this page
Indexing hint: Animal study · 2005
6 results
Activity-dependent neurotrophic factor-9 and NAP promote neurite outgrowth in rat hippocampal and cortical cultures.
Smith-Swintosky et al. 2005Journal of molecular neuroscience : MNcited by 52
PMID 15800376DOI 10.1385/jmn:25:3:225PUB-15800376
Full text at the publisher6 results
Indexing hint: Animal study · 2004
5 results
Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze.
Alcalay et al. 2004Neuroscience letterscited by 68
PMID 15135910DOI 10.1016/j.neulet.2003.12.005PUB-15135910
Full text at the publisher5 results
Indexing hint: Animal study · 2004
6 results
The femtomolar-acting NAP interacts with microtubules: Novel aspects of astrocyte protection.
Gozes et al. 2004Journal of Alzheimer's disease : JADcited by 62
PMID 15665412DOI 10.3233/jad-2004-6s605PUB-15665412
Full text at the publisher6 results
More studies
1 study on this page
Indexing hint: Animal study · 1989
Vasoactive intestinal peptide potentiates sexual behavior: inhibition by novel antagonist.
Gozes et al. 1989Endocrinologycited by 82
PMID 2583049DOI 10.1210/endo-125-6-2945PUB-02583049
Full text at the publisher
Other registry references
References listed at the registry that are not in PepBank. They link to PubMed.
- DerivedGeorgiades A, Davis VG, Atkins AS, Khan A, Walker TW, Loebel A, Haig G, Hilt DC, Dunayevich E, Umbricht D, Sand M, Keefe RSE. Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients. Schizophr Res. 2017 Dec;190:172-179. doi: 10.1016/j.schres.2017.03.040. Epub 2017 Apr 20. PMID 28433500
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years up to 60 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
* 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)
* Able to complete the baseline MCCB validly as assessed by Chief Neuropsychologist or NP tester
* Raw score of 6 or greater on the WTAR
Exclusion Criteria:
* 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.
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