Optimisation of Antipsychotic Drug Use in Older People

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by Institute of Psychiatry, London
Sponsor:
Information provided by (Responsible Party):
Suzanne Reeves, Institute of Psychiatry, London
ClinicalTrials.gov Identifier:
NCT01454453
First received: October 12, 2011
Last updated: August 8, 2012
Last verified: August 2012
  Purpose

Drugs such as amisulpride, known as antipsychotic drugs, are used to treat troublesome and distressing symptoms in older people. Although these drugs can be beneficial, they are associated with side effects, particularly in patients with dementia and schizophrenia- like illness. There is an urgent clinical need to understand why this is the case, to guide treatment strategies.

This study aims to utilise brain imaging techniques that measure the action of antipsychotic drugs in the brain to explore the causes of this susceptibility in older people with dementia and schizophrenia-like illness, and translate these findings into direct patient benefit.

The first aim is to establish whether people with dementia have an increased risk of side effects because more of the drug gains access to the brain. This will be tested using a low (starter) dose of the commonly prescribed drug amisulpride and comparing people with dementia with two other groups - healthy participants and people with schizophrenia-like illness.

The second aim is to investigate and compare the relationship between the action of amisulpride at brain sites and clinical response (symptom reduction and side effect profile) during the first 10 weeks of amisulpride treatment in the two patient groups.

Patients involved in the brain imaging studies described above will also have information on drug dosage, levels of drug in the bloodstream and clinical response collected as drug dose is increased over a 10 week period.

The information gathered from these studies will help us to establish the minimum clinically effective dose and optimum dose range of amisulpride required to treat symptoms without side effects. An understanding of how the action of drugs like amisulpride at brain sites relates to clinical response will also help us to make predictions about the prescribing of other antipsychotic drugs to the two patient groups.


Condition Intervention Phase
Alzheimer's Disease
Schizophrenia
Drug: amisulpride
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rationalisation of Antipsychotic Drug Use in Older People, Using [18F]-Fallypride PET

Resource links provided by NLM:


Further study details as provided by Institute of Psychiatry, London:

Primary Outcome Measures:
  • Dopamine D2/3 receptor occupancy at steady state (4 days) treatment with 50mg amisulpride [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    (i) To investigate the relationship between plasma levels and regional D2/3 receptor occupancy following steady state (4 days) treatment with a fixed dose (50mg) of amisulpride within 3 groups: Healthy controls (HC), AD and SLP (20 in each group).

  • Dopamine D2/3 receptor occupancy during 4-10 weeks treatment with 50-200mg amisulpride [ Time Frame: 4-10 weeks ] [ Designated as safety issue: No ]
    (ii) To investigate the relationship between plasma kinetics, regional D2/3 receptor occupancy and therapeutic and adverse effect profile in patients with SLP and AD (20 in each group) during 4-10 weeks treatment with amisulpride (50-200mg daily).


Secondary Outcome Measures:
  • neuropsychological test performance [ Time Frame: 4-10 weeks ] [ Designated as safety issue: No ]
    Changes in neuropsychological test performance after 4-10 weeks amisulpride treatment


Estimated Enrollment: 120
Study Start Date: May 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy participants
4 days (steady state) treatment
Drug: amisulpride
4 days treatment 50 mg daily
Experimental: Patients - steady state treatment
Amisulpride treatment group, brain imaging carried out pre and post 4 days treatment, does titration continues for up to 10 weeks
Drug: amisulpride
4 days treatment, 50mg daily
No Intervention: Patients - control group
Control group, no treatment
Experimental: Patients - dose titration
Treatment group, brain imaging carried out pre and post 4-10 weeks treatment
Drug: amisulpride
4-10 weeks treatment, 50-200mg daily

  Eligibility

Ages Eligible for Study:   60 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

Treatment Group

Healthy controls

  • aged between 60 and 95 years of age
  • score <6 on the Geriatric depression scale
  • score >26/30 on the Mini Mental State Examination

Treatment and Control Group

Schizophrenia

  • meet diagnostic criteria for schizophrenia-like illness
  • aged between 60 and 95 years of age
  • score <6 on the Geriatric depression scale

Alzheimer's

  • meet diagnostic criteria for AD
  • score <=4 on the Modified Hachinski Ischaemia Scale
  • score < 8 on a modified version of the UPDRS
  • aged between 60 and 95 years of age
  • score <6 on the Geriatric depression scale

Exclusion Criteria

Treatment Group

Healthy controls

  • current or past psychiatric illness, traumatic brain injury or epilepsy
  • medical conditions that might affect ability to tolerate a brain scan
  • prescribed any drug that interferes with brain dopamine in past 2 weeks (6 weeks if depot antipsychotic medication).
  • unable to give informed consent

Schizophrenia

  • current or past history of addiction, traumatic brain injury or epilepsy
  • prescribed any drug that interferes with brain dopamine in past 2 weeks (6 weeks if depot antipsychotic medication).
  • medical conditions that might affect Ability to tolerate a brain scan
  • unable to give informed consent

Alzheimer's

  • current or past history of psychiatric illness, traumatic brain injury or epilepsy
  • prescribed an antipsychotic or other oral drug that interferes with brain dopamine function within the past 2 weeks (6 weeks if depot antipsychotic medication).
  • medical conditions that might affect a person's ability to tolerate a brain scan

Control Group

Schizophrenia

  • change in psychotropic prescribing (2 weeks for oral medication, 6 weeks for depot)
  • unable to give informed consent

Alzheimer's

• change in psychotropic prescribing (2 weeks for oral medication, 6 weeks for depot)

  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: NCT01454453

Contacts
Contact: Suzanne J Reeves, MBChB, PhD 020 7848 0002 ext 0548 suzanne.j.reeves@kcl.ac.uk
Contact: Robert J Howard, MBBS, MD 020 7848 0002 ext 0545 robert.j.howard@kcl.ac.uk

Locations
United Kingdom
Institute of Psychiatry, Kings College London Recruiting
London, United Kingdom, SE58AF
Principal Investigator: Suzanne J Reeves, MBChB PhD         
Sponsors and Collaborators
Institute of Psychiatry, London
Investigators
Principal Investigator: Suzanne J Reeves, MBChB, PhD Institute of Psychiatry, London
  More Information

Additional Information:
No publications provided

Responsible Party: Suzanne Reeves, Clinician Scientist, Institute of Psychiatry, London
ClinicalTrials.gov Identifier: NCT01454453     History of Changes
Other Study ID Numbers: 2167SR
Study First Received: October 12, 2011
Last Updated: August 8, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Institute of Psychiatry, London:
amisulpride
receptor occupancy
antipsychotic sensitivity

Additional relevant MeSH terms:
Alzheimer Disease
Schizophrenia
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Sultopride
Sulpiride
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on July 28, 2014