Adjuvant Therapy With Pergolide in Treating Cognitive Deficits in Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by:
Heidelberg University
ClinicalTrials.gov Identifier:
NCT01066403
First received: February 9, 2010
Last updated: NA
Last verified: December 2008
History: No changes posted
  Purpose

The objective of this study is to compare the modulation of pergolide, a D1/D2 receptor agonist, to placebo in non-acute schizophrenic subjects under concomitant therapy with atypical antipsychotics on specific PFC functions. Further aims are to assess the influence of pergolide on psychopathology and extrapyramidal symptoms in comparison to placebo.


Condition Intervention
Schizophrenia
Drug: Pergolide

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Dopaminergic Modulation of Prefrontal Functions in Schizophrenic Patients: Adjuvant Therapy With Pergolide

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • The D1-specific dopaminergic modulation of prefrontal functions (executive control, working memory, control of semantic association) confirmed by a complex neuropsychological battery including a non - PFC activating control task [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Influence of pergolide on psychopathology symptoms and extrapyramidal symptoms in comparison to placebo measured by specific rating scales, e.g. PANSS and Calgary Depression Scale [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: October 2003
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pergolide
Patients will be randomly assigned to a sequence of treatments of either pergolide or placebo p.o. under continuous concomitant atypical neuroleptic therapy (stable at least 2 weeks prior trial begin).
Drug: Pergolide

0,3 mg pergolide (the first two days begin with 0,05mg, then increase of dose of 0,1mg every 3 days for a maximum of 0,3mg/d, taken orally 3x 0,1mg/day). Then stable dose of 0,3mg for one week.. Subsequently slow (for 8 days) reduction of dosage of 0,1mg every 3 days for 6 days then 0,05mg every day for the last two days.

Placebo group is identical in appearance and number of placebo capsules, in the same starting and maintenance scheme as for the pergolide group.

Other Names:
  • Parkotil
  • Pergolid

Detailed Description:

Additionally to the desired treatment of positive symptoms, the administration of typical neuroleptics can lead to undesired side effects such as increase of negative symptomatic and cognitive deficits. The influence of atypical neuroleptics on cognition is still not very well studied. Furthermore there is evidence that some cognitive symptoms seen in schizophrenia are related to a disturbance in the prefrontal cortex PFC and involve specific subtypes of dopamine receptors, namely D1 subtypes, which predominates in this area. It is assumed that patients with this spectrum of cognitive deficits have the worse course and prognosis. Furthermore these deficits are more therapy resistant to the conventional current therapy approaches. There is however some evidence pointing to a positive influence of dopamine agonists on these deficits, but the selective effect of dopamine sub-receptors is still not well investigated. The aim of the study is to examine whether cognitive deficits in higher cognitive functions of the PFC such as working memory, semantic association and executive control improves under dopamine agonistic therapy in schizophrenia and whether this is related to selective D1 modulation.

We predict that the modulation of D1 subtype receptors improve performance in each of these tasks. Because there is no D1 agonist available for human research we decided to use a design comparing a dopamine agonist with mixed D1 and D2 agonistic properties (pergolide) to placebo under a stable D2 antagonistic continuous-therapy with atypical antipsychotics. With this design the D2-component of pergolide can be antagonized by the atypical antipsychotics and a D1 agonistic effect can be suggested, as well as protecting patients against a psychotic re-exacerbation. With this study we aim to bring more insight in the therapy of PFC cognitive deficits of schizophrenia by helping to elucidate the role of selective agonists on cognition in schizophrenic patients. I

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-acute in- and outpatients, with predominantly negative symptoms, and remitted from positive symptoms like hallucinations and delusions for 1 week, with the diagnosis of schizophrenia (ICD 10: F20) at the Psychiatry Hospital of the Universities of Heidelberg, Hamburg-Eppendorf, Zentralinstitut für Seelische Gesundheit Mannheim, SRH Klinikum Karlsbad - Langensteinbach (Clinical interview to establish diagnosis with DSM-IV (M.I.N.I International Neuropsychiatric Interview _ German Version 5.0.0)
  • Verbal IQ higher than 80, as measured by the Mehrfachwahl-Wortschatz-Intelligenztest
  • Visual acuity must be normal or corrected.
  • Color sight intact
  • Positive neuroleptics drug monitoring level
  • Females must be under adequate contraception (oral hormonal contraceptive, IntraUterineDevice)

Exclusion Criteria:

  • Concomitant neurologic and internistic diseases (especially cardiovascular diseases and others like untreated thyroid hyper-/hypofunction, liver or kidney dysfunction, seizures or history of traumatic brain injury)
  • Known allergy reaction under ergoline-therapy
  • Actual history of drug abuse/addiction, concomitant other psychiatric disorder (screened by SCID) and suicide attempt in the medical history
  • Other long term pharmacological treatment which can interact with dopamine agonists and antagonists (e.g. anticoagulants, digitoxin)
  • Pregnancy and breastfeeding (anamneses and pregnancy test in urine)
  • Participation in other clinical trial for the last 3 months
  • History of malignant neuroleptic syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01066403

Locations
Germany
Zentralinstitut für Seelische Gesundheit
Mannheim, 68159, Germany
Psychiatrische Universitätsklinik
Heidelberg, BW, Germany, 69115
Universitätsklinikum Hamburg - Eppendorf
Hamburg, Germany, 20246
SRH Klinikum Karlsbad - Langensteinbach gGmbH
Karlsbad, Germany, 76307
Sponsors and Collaborators
Heidelberg University
Stanley Medical Research Institute
Investigators
Principal Investigator: Daniela Roesch - Ely, MD Psychiatrische Universitätsklinik Heidelberg
  More Information

Additional Information:
No publications provided

Responsible Party: Daniela Roesch Ely, PI, University of Heidelberg
ClinicalTrials.gov Identifier: NCT01066403     History of Changes
Other Study ID Numbers: 03T-342-DRE
Study First Received: February 9, 2010
Last Updated: February 9, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heidelberg University:
schizophrenia
cognitive deficits
dopamine
dopamine agonists
prefrontal cortex
D1 specific modulation
pergolide
executive control
working memory
Influence of pergolide on cognition in Schizophrenia
D1-specific modulation of prefrontal functions
Influence of pergolide on psychopathology and depression
Influence of pergolide on extrapyramidal symptoms

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Pergolide
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014