SchizophreniaPhase 2AL-108NCT00505765
A Multicenter Study of NAP (AL-108) in Schizophrenia
A Phase 2 study testing AL-108 in people with Schizophrenia, run by University of California, Los Angeles at 8 sites in United States.
Trial 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.). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- AL-108
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 8 sitesUnited States
- Study dates
- Jul 2007to Apr 2009
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 17Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Harvard Medical School
Boston, Massachusetts, 02215
Maryland Psychiatric Research Center
Catonsville, Maryland, 21228
Duke University Medical Center
Durham, North Carolina, 27710
UCLA
Los Angeles, California, 90073
Columbia University Medical Center
New York, New York, 10032
Nathan Kline Institute
Orangeburg, New York, 10962
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Multicenter Ascending Dose, Double Blind, Placebo-controlled Study of NAP (AL-108) in Chronic Schizophrenia
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.
Read the detailed description
Background
AL-108 is an intranasal drug product containing NAP, an 8 amino-acid peptide (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln; NAPVSIPQ, MW=824.9) fragment of the much larger (approx. 124KD) Activity-Dependent Neuroprotective Protein (ADNP), which participates in neurodevelopment and neuroprotection. In mice, ADNP knockouts are lethal exhibiting CNS dysgenesis. ADNP mediates its effects in part through interaction with microtubules. Because of its large size, ADNP is assumed to not penetrate the BBB and thus cannot be used pharmacologically. NAP was chosen because it represents the epitope most associated with microtubule interaction and neuroprotection. NAP is absorbed following IV or intranasal administration, and has been shown to cross the BBB.
Rationale for NAP treatment: tubulin function in brain function
The cytoskeleton plays a key role in maintaining the highly asymmetrical shape and structural polarity of neurons that are essential for neuronal physiology. The cytoskeleton is made up of microfilaments, intermediate filaments and microtubules. Microfilaments (4-9 nm diameter) are made up of actin monomers and they function mainly to provide mechanical support and locomotion to the cell. Intermediate filaments are cytoplasmic fibers of ~10nm diameter. They provide supporting framework within the cell. Microtubules (~24nm diameter) consist of tubulin and microtubule associate proteins. They function to transport nutrients and chemical messengers along the cell. Neurofibrillary tangles are twisted bundles of neurofibrils formed when the microtubule-associated protein, tau, dissociates from microtubules and clusters to form an insoluble mass. Under normal conditions tau binds to microtubules, stabilizing neuronal structure and integrity.
Hyperphosphorylation of tau is assumed to be the cause for the formation of neurofibrillary tangles. Although neurofibrillary tangles are most associated with cognitive dysfunction in Alzheimers disease, some increase in neurofibrillary pathology has also been reported in schizophrenia, potentially as consequence of antipsychotic medication (1). Thus, mechanisms underlying microtubular function may be relevant to schizophrenia as well. In association with tubulin polymerization into microtubules, NAP influences tau dynamics by increasing the ratio of non-phosphorylated tau to phosphorylated tau, implying a dynamic process of cellular maintenance of the microtubular network, which is essential for the survival of the cell.
In brain, tubulin frameworks are stabilized by recently described STOP proteins (2) (aka MAP6). Linkages to allelic variation in STOP genes has been reported in schizophrenia, along with altered STOP protein expression in some brain regions (3). STOP knockdown mice show disturbances in dopaminergic neurotransmission (4) along with deficits in PPI and hypermotility that were partially reversed with clozapine (5). Thus, neuropathological features of schizophrenia may be due, in part, to abnormal STOP-related stabilization of microtubular structure, and NAP may stabilize STOP-related abnormal neurophysiological processes in schizophrenia.
- Conditions
- Schizophrenia
- Being tested
- AL-108, Placebo
- Keywords
- Cognition, Schizophrenia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL-108Drug
AL-108, 5 mg/day- one spray in each nostril once per day
AL-108Drug
AL-108, 30 mg/day- 3 sprays in each nostril, twice per day
PlaceboDrug
Placebo- 3 sprays in each nostril, twice per day
PlaceboDrug
Placebo- one spray in each nostril, once per day
| Study group | Role | What they receive |
|---|---|---|
| AL-108, 30 mg/day | Experimental | AL-108, 30 mg/day- 3 sprays in each nostril, twice per day Receives: Drug: AL-108 |
| AL-108, 5 mg/day | Experimental | AL-108, 5 mg/day- one spray in each nostril once per day Receives: Drug: AL-108 |
| Placebo, 3 sprays BID | Placebo comparator | Placebo- 3 sprays in each nostril, twice per day Receives: Drug: Placebo |
| Placebo, 1 Spray Daily | Placebo comparator | Placebo- one spray in each nostril, once per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Baseline, 12 weeks
Secondary outcomes (4)
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
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.
Measured: Baseline, week 6
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
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.
Measured: Baseline, 12 weeks
Change in SCoRS Interviewer Global Rating
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.
Measured: Baseline, 6 weeks
Change in SCoRS Interviewer Global Rating
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.
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2007 (estimated)
- Study startJul 2007
- Primary completionApr 2009
- Study completionApr 2009
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 (26)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 California, Los AngelesThe 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, Washington University School of Medicine, Massachusetts General Hospital, Nathan Kline Institute for Psychiatric Research, Columbia University, Duke University, Beth Israel Deaconess Medical Center
- Responsible party
- Sponsor
- Investigators
- Daniel C Javitt, MD, PhD, Principal investigator, Nathan Kline Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00505765
- Sponsor's protocol ID
- TURNS03
- Other IDs
- HHSN 278200441003C
- Acronym
- AL-108
- Status last verified
- Jan 2017
- First submitted
- 20 Jul 2007
- Last updated
- 10 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
McMahon RP, Arndt S, Conley RR. More powerful two-sample tests for differences in repeated measures of adverse effects in psychiatric trials when only some patients may be at risk. Stat Med. 2005 Jan 15;24(1):11-21. doi: 10.1002/sim.1837.
PubMed 15515151Edwards D, Madsen J. Constructing multiple test procedures for partially ordered hypothesis sets. Stat Med. 2007 Dec 10;26(28):5116-24. doi: 10.1002/sim.2905.
PubMed 17476650Jackman AH, Doty RL. Utility of a three-item smell identification test in detecting olfactory dysfunction. Laryngoscope. 2005 Dec;115(12):2209-12. doi: 10.1097/01.mlg.0000183194.17484.bb.
PubMed 16369168Gozes I, Divinski I. The femtomolar-acting NAP interacts with microtubules: Novel aspects of astrocyte protection. J Alzheimers Dis. 2004 Dec;6(6 Suppl):S37-41. doi: 10.3233/jad-2004-6s605.
PubMed 15665412Rothermundt M, Arolt V, Bayer TA. Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun. 2001 Dec;15(4):319-39. doi: 10.1006/brbi.2001.0648.
PubMed 11782102Rapaport MH, Delrahim KK. An abbreviated review of immune abnormalities in schizophrenia. CNS Spectr. 2001 May;6(5):392-7. doi: 10.1017/s1092852900021763.
PubMed 15999027Kelly DL, Conley RR. A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology. 2006 Apr;31(3):340-6. doi: 10.1016/j.psyneuen.2005.08.010. Epub 2005 Sep 28.
PubMed 16198059Gozes I, Meltzer E, Rubinrout S, Brenneman DE, Fridkin M. Vasoactive intestinal peptide potentiates sexual behavior: inhibition by novel antagonist. Endocrinology. 1989 Dec;125(6):2945-9. doi: 10.1210/endo-125-6-2945.
PubMed 2583049Rotstein M, Bassan H, Kariv N, Speiser Z, Harel S, Gozes I. NAP enhances neurodevelopment of newborn apolipoprotein E-deficient mice subjected to hypoxia. J Pharmacol Exp Ther. 2006 Oct;319(1):332-9. doi: 10.1124/jpet.106.106898. Epub 2006 Jul 5.
PubMed 16822898Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003 Jul 31;39(3):409-21. doi: 10.1016/s0896-6273(03)00434-3.
PubMed 12895417Braga RJ, Mendlowicz MV, Marrocos RP, Figueira IL. Anxiety disorders in outpatients with schizophrenia: prevalence and impact on the subjective quality of life. J Psychiatr Res. 2005 Jul;39(4):409-14. doi: 10.1016/j.jpsychires.2004.09.003. Epub 2004 Nov 13.
PubMed 15804391Alcalay RN, Giladi E, Pick CG, Gozes I. Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze. Neurosci Lett. 2004 May 6;361(1-3):128-31. doi: 10.1016/j.neulet.2003.12.005.
PubMed 15135910Gozes I, Alcalay R, Giladi E, Pinhasov A, Furman S, Brenneman DE. NAP accelerates the performance of normal rats in the water maze. J Mol Neurosci. 2002 Aug-Oct;19(1-2):167-70. doi: 10.1007/s12031-002-0028-0.
PubMed 12212775Gozes I, Giladi E, Pinhasov A, Bardea A, Brenneman DE. Activity-dependent neurotrophic factor: intranasal administration of femtomolar-acting peptides improve performance in a water maze. J Pharmacol Exp Ther. 2000 Jun;293(3):1091-8.
PubMed 10869414Ito M, Depaz I, Wilce P, Suzuki T, Niwa S, Matsumoto I. Expression of human neuronal protein 22, a novel cytoskeleton-associated protein, was decreased in the anterior cingulate cortex of schizophrenia. Neurosci Lett. 2005 Apr 22;378(3):125-30. doi: 10.1016/j.neulet.2004.12.079.
PubMed 15781144
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Ascending Dose, Double Blind, Placebo-controlled Study of NAP (AL-108) in Chronic Schizophrenia
- ClinicalTrials.gov ID
- NCT00505765
- Acronym / sponsor ID
- AL-108 / TURNS03
- Conditions
- Schizophrenia
- Keywords
- Cognition, Schizophrenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- University of Maryland, Washington University School of Medicine, Massachusetts General Hospital, Nathan Kline Institute for Psychiatric Research, Columbia University, Duke University, Beth Israel Deaconess Medical Center
- Study start
- Jul 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 23 Jul 2007 (estimated)
- Results
- Posted 27 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background
AL-108 is an intranasal drug product containing NAP, an 8 amino-acid peptide (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln; NAPVSIPQ, MW=824.9) fragment of the much larger (approx. 124KD) Activity-Dependent Neuroprotective Protein (ADNP), which participates in neurodevelopment and neuroprotection. In mice, ADNP knockouts are lethal exhibiting CNS dysgenesis. ADNP mediates its effects in part through interaction with microtubules. Because of its large size, ADNP is assumed to not penetrate the BBB and thus cannot be used pharmacologically. NAP was chosen because it represents the epitope most associated with microtubule interaction and neuroprotection. NAP is absorbed following IV or intranasal administration, and has been shown to cross the BBB.
Rationale for NAP treatment: tubulin function in brain function
The cytoskeleton plays a key role in maintaining the highly asymmetrical shape and structural polarity of neurons that are essential for neuronal physiology. The cytoskeleton is made up of microfilaments, intermediate filaments and microtubules. Microfilaments (4-9 nm diameter) are made up of actin monomers and they function mainly to provide mechanical support and locomotion to the cell. Intermediate filaments are cytoplasmic fibers of ~10nm diameter. They provide supporting framework within the cell. Microtubules (~24nm diameter) consist of tubulin and microtubule associate proteins. They function to transport nutrients and chemical messengers along the cell. Neurofibrillary tangles are twisted bundles of neurofibrils formed when the microtubule-associated protein, tau, dissociates from microtubules and clusters to form an insoluble mass. Under normal conditions tau binds to microtubules, stabilizing neuronal structure and integrity.
Hyperphosphorylation of tau is assumed to be the cause for the formation of neurofibrillary tangles. Although neurofibrillary tangles are most associated with cognitive dysfunction in Alzheimers disease, some increase in neurofibrillary pathology has also been reported in schizophrenia, potentially as consequence of antipsychotic medication (1). Thus, mechanisms underlying microtubular function may be relevant to schizophrenia as well. In association with tubulin polymerization into microtubules, NAP influences tau dynamics by increasing the ratio of non-phosphorylated tau to phosphorylated tau, implying a dynamic process of cellular maintenance of the microtubular network, which is essential for the survival of the cell.
In brain, tubulin frameworks are stabilized by recently described STOP proteins (2) (aka MAP6). Linkages to allelic variation in STOP genes has been reported in schizophrenia, along with altered STOP protein expression in some brain regions (3). STOP knockdown mice show disturbances in dopaminergic neurotransmission (4) along with deficits in PPI and hypermotility that were partially reversed with clozapine (5). Thus, neuropathological features of schizophrenia may be due, in part, to abnormal STOP-related stabilization of microtubular structure, and NAP may stabilize STOP-related abnormal neurophysiological processes in schizophrenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AL-108, 30 mg/day | Experimental | Drug: AL-108AL-108, 30 mg/day- 3 sprays in each nostril, twice per day |
| AL-108, 5 mg/day | Experimental | Drug: AL-108AL-108, 5 mg/day- one spray in each nostril once per day |
| Placebo, 3 sprays BID | Placebo comparator | Drug: PlaceboPlacebo- 3 sprays in each nostril, twice per day |
| Placebo, 1 Spray Daily | Placebo comparator | Drug: PlaceboPlacebo- one spray in each nostril, once per day |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- DSM IV/DSM IV TR diagnosis of schizophrenia
- Capable of providing informed consent
- Males and Females
- Age: 18 and 60
- Caucasian or Non Caucasian
Key exclusion criteria (13 listed)
- 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:
- 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.
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 |
|---|---|---|
| AL-108AL-108, 5 mg/day- one spray in each nostril once per day | Drug | AL-108, 5 mg/day |
| AL-108AL-108, 30 mg/day- 3 sprays in each nostril, twice per day | Drug | AL-108, 30 mg/day |
| PlaceboPlacebo- 3 sprays in each nostril, twice per day | Drug | Placebo, 3 sprays BID |
| PlaceboPlacebo- one spray in each nostril, once per day | Drug | Placebo, 1 Spray Daily |
Primary outcome
Change in MATRICS Consensus Cognitive Battery Composite Score Change
Time frame: Baseline, week 6
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
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).
4 secondary outcomes
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
Time frame: Baseline, week 6
Change in UCSD Performance-Based Skills Assessment (UPSA) Summary Scores
Time frame: Baseline, 12 weeks
Change in SCoRS Interviewer Global Rating
Time frame: Baseline, 6 weeks
Change in SCoRS Interviewer Global Rating
Time frame: Baseline, 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15515151McMahon RP, Arndt S, Conley RR. More powerful two-sample tests for differences in repeated measures of adverse effects in psychiatric trials when only some patients may be at risk. Stat Med. 2005 Jan 15;24(1):11-21. doi: 10.1002/sim.1837.
- Background: PubMed 17476650Edwards D, Madsen J. Constructing multiple test procedures for partially ordered hypothesis sets. Stat Med. 2007 Dec 10;26(28):5116-24. doi: 10.1002/sim.2905.
- Background: PubMed 16369168Jackman AH, Doty RL. Utility of a three-item smell identification test in detecting olfactory dysfunction. Laryngoscope. 2005 Dec;115(12):2209-12. doi: 10.1097/01.mlg.0000183194.17484.bb.
- Background: PubMed 15665412Gozes I, Divinski I. The femtomolar-acting NAP interacts with microtubules: Novel aspects of astrocyte protection. J Alzheimers Dis. 2004 Dec;6(6 Suppl):S37-41. doi: 10.3233/jad-2004-6s605.
- Background: PubMed 11782102Rothermundt M, Arolt V, Bayer TA. Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun. 2001 Dec;15(4):319-39. doi: 10.1006/brbi.2001.0648.
- Background: PubMed 15999027Rapaport MH, Delrahim KK. An abbreviated review of immune abnormalities in schizophrenia. CNS Spectr. 2001 May;6(5):392-7. doi: 10.1017/s1092852900021763.
- Background: PubMed 16198059Kelly DL, Conley RR. A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology. 2006 Apr;31(3):340-6. doi: 10.1016/j.psyneuen.2005.08.010. Epub 2005 Sep 28.
- Background: PubMed 2583049Gozes I, Meltzer E, Rubinrout S, Brenneman DE, Fridkin M. Vasoactive intestinal peptide potentiates sexual behavior: inhibition by novel antagonist. Endocrinology. 1989 Dec;125(6):2945-9. doi: 10.1210/endo-125-6-2945.
- Background: PubMed 16822898Rotstein M, Bassan H, Kariv N, Speiser Z, Harel S, Gozes I. NAP enhances neurodevelopment of newborn apolipoprotein E-deficient mice subjected to hypoxia. J Pharmacol Exp Ther. 2006 Oct;319(1):332-9. doi: 10.1124/jpet.106.106898. Epub 2006 Jul 5.
- Background: PubMed 12895417Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003 Jul 31;39(3):409-21. doi: 10.1016/s0896-6273(03)00434-3.
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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.
Daniel C Javitt, MD, PhD principal investigator
Nathan Kline Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AL-108 in people with Schizophrenia, run by University of California, Los Angeles at 8 sites 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 17 inclusion and 13 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 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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 27 Jan 2017). 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?
Change in MATRICS Consensus Cognitive Battery Composite Score Change (time frame: Baseline, week 6). The study lists 2 primary outcomes in all. 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 NCT00505765, which also lists 26 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 10 Mar 2017.