Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia

NCT01246232 | Completed Phase 4 DMC

• 3 other identifiers: CRO1498HTA 08/116/122010-018963-40
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 3

Brief Summary

Schizophrenia is a mental health problem usually starting in the late teens/early twenties, and often lasting many years. The standard medication ('antipsychotics') for this problem is usually helpful, and if taken continually can keep people well, reducing the likelihood of further episodes. However, in up to one in three people with schizophrenia, the illness does not show much improvement with antipsychotic medication. For some of these 'resistant' illnesses, one particular antipsychotic, clozapine, can work well, but one disadvantage is the risk of a severe blood side effect which means that regular blood testing is necessary. If the response to clozapine treatment is disappointing, there is some evidence that adding another antipsychotic can sometimes produce more improvement. However, it seems that the added antipsychotic may need to be taken by the person for at least 10 weeks in order to work well. The investigators plan to test carefully the possible benefits and problems when the antipsychotic amisulpride or a dummy tablet ('placebo') is added to clozapine for 12 weeks in people whose schizophrenia illness has not been helped much by any antipsychotic medication on its own, and who are now taking clozapine, but again with not much improvement. The investigators have chosen amisulpride because its pharmacological action may be complementary to that of clozapine, and also it is less likely than some other antipsychotics to compound some of the characteristic side effects of clozapine, such as sedation, weight gain and other metabolic problems. Adjunctive amisulpride or placebo will be randomly assigned. The investigators expect that adding amisulpride will be more likely to cause an improvement than adding placebo. But the investigators should learn more about the risks and side effects of combining these two medications. Also, the investigators should gain a greater understanding of the possible benefits of adding another antipsychotic to clozapine in relation to particular problem symptoms, and a person's ability to live and work in the community.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Total score on the Positive and Negative Syndrome Scale

  Baseline, and 6 and 12 weeks

Secondary Outcomes (5)

• Social and Occupational Functioning Assessment Scale

  Baseline, and 6 and 12 weeks

• Calgary Depression Rating Scale for Schizophrenia

  Baseline, and 6 and 12 weeks

• Schedule for the Assessment of Insight

  Baseline, and 6 and 12 weeks

• Service Engagement Scale

  Baseline, and 6 and 12 weeks

• Antipsychotic Non-Neurological Side Effects Scale

  Baseline, and 6 and 12 weeks

Study Arms (2)

Amisulpride

EXPERIMENTAL

400mg, 2 x 200mg amisulpride capsules for the first 4 weeks, then the option of titrating up to 800mg, 4 x 200mg amisulpride capsules for the remaining 8 weeks.

Drug: Amisulpride

Placebo

PLACEBO COMPARATOR

400mg, 2 x 200mg amisulpride capsules, or 2 matching placebo capsules for the first 4 weeks, then the option of titrating up to 800mg, 4 x 200mg amisulpride capsules, or 4 matching placebo capsules for the remaining 8 weeks.

Drug: placebo

Interventions

Amisulpride DRUG

Clozapine augmentation with another second-generation antipsychotic, amisulpride (400mg amisulpride for the first 4 weeks, then the option of titrating up to 800mg amisulpride for the remaining 8 weeks).

Amisulpride

placebo DRUG

Clozapine augmentation with 1 capsule placebo for the first 4 weeks, then the option of titrating up to 2 capsules placebo for the remaining 8 weeks).

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A criterion level of persistent symptom severity despite an adequate trial of clozapine monotherapy in terms of dosage, duration and adherence (as used by Honer et al 2006):
• Treatment for at least 12 weeks at a stable dose of 400 mg or more of clozapine a day, unless the size of the dose was limited by side effects
• A total score of 80 or greater at baseline on the Positive and Negative Syndrome Scale (PANSS: Kay et al 1987, 1988); the range of possible scores is 30 to 210, with higher scores indicating more severe symptoms.
• A Clinical Global Impressions (CGI: Guy 1976) score of 4 or greater (range of possible scores, 1=not mentally ill to 7=extremely ill)
• A Social and Occupational Functioning Assessment Scale (SOFAS: Goldman et al 1992, DSM-IV 1994) score of 40 or less; range of possible scores, 1 to 100, with lower scores indicating impaired functioning.
• Age 18-65 years, inclusive
• Clinically stable for the last 3 months with a consistent clozapine regimen.
• Competent and willing to provide written, informed consent.

You may not qualify if:

• Clinically-significant alcohol/substance use in the previous three months
• Developmental disability
• Indication for current treatment with clozapine was intolerance/movement disorder
• A previous trial of clozapine augmentation with amisulpride.
• Existing relevant physical health problems: such as cardiovascular disease, previous problems with prolactin, and impaired liver/ renal function.
• Any woman who is pregnant or planning a pregnancy, and any woman of child bearing potential unless using adequate contraception.

Sponsors & Collaborators

• Imperial College London: lead
• University of Manchester: collaborator
• University College, London: collaborator

Study Sites (3)

University College London

London, NW3 2PF, United Kingdom

Location

Imperial College London

London, W6 8LN, United Kingdom

Location

University of Manchester

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Amisulpride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Thomas R Barnes, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: November 23, 2010
• Study Start: September 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 1, 2015

Record last verified: 2011-09

Locations

GB (3)