Rasagiline in the Treatment of Persistent Negative Symptoms of Schizophrenia

NCT00492336 | Completed Phase 4 Results DMC

• 2 other identifiers: HP-00043807H-27877
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 5

Brief Summary

This is a study of a new medication for the treatment of cognitive impairments (thinking difficulties) and negative symptoms in people with schizophrenia. The new medication is rasagiline. Rasagiline is a drug which has been approved by the Food and Drug Administration for the treatment of Parkinson's disease. It is used to treat cognitive problems.

Conditions

Schizophrenia

Keywords

Cognitive impairments; Negative symptoms

Outcome Measures

Primary Outcomes (5)

• Change in Negative Symptoms

  The Scale for the Assessment of Negative Symptoms (SANS) rating scale was used to assess the negative symptoms of schizophrenia. Scores on the subscales are combined (summed) to compute a total score. There are a total of 17 subscales. Each subscale ranges from 0="Not at all" to 5="Severe". Every 4 weeks the summed subscale scores provide a total score for that week (0-85). Higher scores indicate more severe negative symptoms.

  Every 4 weeks over a 12 week period

• Cognitive Testing - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score

  The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160.

  Beginning of treatment phase (week 0) and end of treatment phase (week 12)

• Cognitive Testing - N-Back Neurocognitive Task

  The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.

  Beginning of treatment phase (week 0) and end of treatment phase (week 12)

• Cognitive Testing - Probabilistic Learning Task

  To assess reward learning, participants used performance feedback to choose the most frequently rewarded item in each of three pairs of stimuli (one pair had reward probabilities: 80% vs 20%; one pair had reward probabilities of 70% vs 30%; one pair had the probabilities of 60% vs 40 %) (PL; Frank et al, 2004). A total of 240 trials were administered so each pair was seen 80 times. Higher scores represent more frequent choices of the optimal stimulus in each pair. The frequencies with which participants repeated an item choice that was rewarded on the previous presentation (win-stay) is also presented as a percentage. Similarly, the lose-shift score is the percentage of times that participants changed their choice for unrewarded items (lose-shift). The win-stay score serves as a measure of the impact of positive feedback on subsequent choices while the lost-shift score serves as a measure of the impact of negative feedback on subsequent choices.

  Beginning of treatment phase (week 0) and end of treatment phase (week 12)

• Cognitive Testing - Delayed Discounting

  The monetary choice questionnaire for hypothetical monetary rewards was used to assess delayed discounting (Kirby et al, 1999). The measure includes 27 items in which participants choose between a smaller, immediate reward (SIR) and a larger, delayed reward (LDR). There are three LDR sizes: small ($25-35), medium ($50-60) and large ($75-85). By examining the pattern of choices that participants make across the set of 27 items it is possible to calculate their delay discounting rate, termed K. The discount rate determines the steepness of the reduction in the present value of a reward with increases in the delay to the possible receipt of that reward. Thus, higher values in K represent greater discounting of the value of future rewards. With this measure K values can range between a low of 0.00016 to a high of 0.25. Higher K values have been linked to measures of impulsivity. Shown in the table are the K values observed when the future rewards were small, medium, or large.

  Beginning of treatment phase (week 0) and end of treatment phase (week 12)

Secondary Outcomes (6)

• Extrapyramidal Symptoms

  Baseline (Week 0) and End of Study (Week 12)

• Number of Participants With Akathisia

  Baseline and every two weeks throughout the double-blind phase of the study, for up to 12 weeks.

• Change in Persistent Positive Symptoms

  Every 4 weeks for 12 weeks.

• Depressive Symptoms

  Every 4 weeks for 12 weeks.

• Global Change in Illness Severity

  Every 4 weeks for 12 weeks.

Study Arms (2)

Rasagiline

ACTIVE COMPARATOR

Treatment with Rasagiline

Drug: rasagiline (Pharmacodynamics)

Inactive pill

PLACEBO COMPARATOR

Treatment with Placebo

Drug: Placebo

Interventions

rasagiline (Pharmacodynamics) DRUG

Rasagiline 1 mg/day for 12 weeks

Rasagiline

Placebo DRUG

Placebo 1 tablet each day

Inactive pill

Eligibility Criteria

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

You may qualify if:

• Subjects will meet DSM-IV criteria for schizophrenia or schizoaffective disorder.
• Current treatment with one or more second generation antipsychotics, except ziprasidone
• On same second generation antipsychotic(s)for at least 56 days
• On same dose of second generation antipsychotic(s)for at least 30 days
• item SANS: Total score (i.e.all items minus global items and poverty of content of speech)greater than 20 or global Rating of Affective Flattening greater than or equal to 3 or global Rating of alogia greater than or equal to 3
• BPRS: Sum of the four positive symptom items less than or equal to 16 (items 4,11,12,15)
• BPRS: Sum of the four Anxiety/Depression Factor items less than or equal to 14 (items 1,2,5,9)
• Simpson-Angus Scale: Total score less than or equal to 8

You may not qualify if:

• DSM-IV Major Depressive Disorder within last 6 months
• Current treatment with ziprasidone
• DSM-IV diagnosis of alcohol or substance dependence within the last 6 months
• DSM-IV criteria for alcohol or substance abuse within the last month
• evidence of illicit substance use, as identified with urine toxicology screen
• History of an organic brain disorder, mental retardation,epilepsy, or a medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol. See those listed below
• Uncontrolled hypertension defined as BP exceeding 145/90 on 3 consecutive readings despite adequate treatment, pheochromocytoma, melanoma, hepatic insufficiency
• Pregnancy or lactation in females
• Pheochromocytoma
• Melanoma
• Hepatic insufficiency

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Stanley Medical Research Institute: collaborator

Study Sites (5)

Baltimore VA Medical Center

Baltimore, Maryland, 21201, United States

Location

Keypoint Mental health Center

Catonsville, Maryland, 21228, United States

Location

Maryland Psychiatric REsearch Center

Catonsville, Maryland, 21228, United States

Location

Mosaic Community Mental health Center

Catonsville, Maryland, 21228, United States

Location

Keypoint Mental health Center

Dundalk, Maryland, 21222, United States

Location

Related Publications (1)

• Buchanan RW, Weiner E, Kelly DL, Gold JM, Keller WR, Waltz JA, McMahon RP, Gorelick DA. Rasagiline in the Treatment of the Persistent Negative Symptoms of Schizophrenia. Schizophr Bull. 2015 Jul;41(4):900-8. doi: 10.1093/schbul/sbu151. Epub 2014 Nov 2.

  PMID: 25368372 DERIVED

MeSH Terms

Conditions

Schizophrenia; Cognitive Dysfunction

Interventions

rasagiline

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Results Point of Contact

• Title: Dr. Robert Buchanan, M.D.
• Organization: Maryland Psychiatric Research Center

rbuchanan@som.umaryland.edu

410-402-7876

Study Officials

• Robert W Buchanan, M.D.

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Maryland Psychiatric Research Center, Outpatient Research Program

Study Record Dates

• First Submitted: June 26, 2007
• First Posted: June 27, 2007
• Study Start: January 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: September 25, 2019
• Results First Posted: June 19, 2013

Record last verified: 2013-06

Locations

US (5)