Phosphodiesterase (PDE) Inhibitors Effect on Cognitive Deficits Associated to Schizophrenia

PDE Inhibitors Effect on Cognitive Deficits Associated to Schizophrenia

Phosphodiesterase (PDE) inhibitors represent a new group of potential antipsychotic compounds currently under development. One of these is papaverine, an inhibitor of the PDE 10 family. The class of PDE10 inhibitors have been reported as possible candidates in the treatment of schizophrenia, and may prove an attractive antipsychotic alternative due to the many side-effects of the currently available antipsychotics. It has been proposed from preclinical studies that PDE10 inhibitors have the potential to reduce cognitive deficits in schizophrenia and these findings need to be confirmed in a human population, in view of the fact that no other currently registered drug posses these unique properties.

The currently proposed project is designed to investigate whether the PDE10 inhibitor Papaverine indeed have the capacity to reduce cognitive deficits in schizophrenia patients. In order to accomplish this effect, Papaverine will be investigated in schizophrenia, with regards to symptomatology, hemodynamic, neurocognition and early information-processing.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia; Cognitive Deficits
• Intervention / Treatment: Drug: Papaverine or placebo

Detailed Description

The study has a double blind, balanced crossover design. Randomized, half of the subjects will be given Papaverine (PDE10 inhibitor, 300 mg orally) in the first session followed by placebo in the second, and the other half will be treated in the reverse order. There is a minimum of one month between the two test-sessions. After each of the two treatments, the subjects will be tested with both a psychophysiological (the Copenhagen Psychophysiological Test-Battery) and neuropsychological test-battery (tests from the Cambridge Neuropsychological Test Automated Battery, or "CANTAB"). The project has three phases: In the first phase 10 healthy subjects will be included to determine the kinetics of Papaverine-contained release capsules ; in the second phase 30 schizophrenia patients and 30 healthy subjects will be included to determine the impact on cognitive and sensory gating related deficits; Finally 10 Healthy subjects will be included to determine the effect of Papaverine on hemodynamical parameters by the means magnetic resonance scannings.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Glostrup psychiatric center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Diagnosed Schizophrenia (WHO ICD 10)
• Treatment stable (no regulation in medicine for 6 weeks prior)
• Mono antipsychotic treatment
• No regular Antidepressants (PN accepted)
• No regular Benzodiazepines (PN accepted)

Exclusion Criteria:

• Dependence syndrome
• Severe physical illness
• MRI incompatible, non removable objects above shoulders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Papaverine; Patients will receive either Papaverine or placebo added to their current medical treatment. Then after one week, they will receive the other treatment (if it was placebo first, then it will be papaverine; if it was papaverine first, then it will be placebo)	Drug: Papaverine or placebo; Papaverine delayed release (depot capsule, 300 mg, orally, one single dosage per subject) or placebo; Other Names: Papaverine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
psychophysiology	Prepulse inhibition of the startle reflex, Mismatch negativity, P300 amplitude	1 hour after intake of capsule with papaverine or placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic changes	Changes in Hemodynamics, as observed by MR techniques	1 hour after intake of capsule with papaverine or placebo

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Glostrup University Hospital, Copenhagen
• Investigators: Study Director: Birte Glenthøj, Professor, University of Copenhagen; Principal Investigator: Mikkel E Sørensen, PHD student, University of Copenhagen; Study Director: Bob Oranje, PHD, Center for Neuropsychiatric Schizophrenia Research

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: March 14, 2013
• First Posted (Estimate): March 19, 2013

Study Record Updates

• Last Update Posted (Estimate): May 28, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Schizophrenia; Cognition; phosphodiesterase inhibitor; Psychophysiology; Papaverine
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Cognitive Dysfunction; Cognition Disorders; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Papaverine
• Other Study ID Numbers: Papaverine schizophrenia