A Biological Basis of Therapy for Negative Symptom Spectrum Disorders: Risperdal Effect on Frontal Metabolism in Asperger's Disorder
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Chang in the Scale for the Assessment of Negative Symptoms (SANS)
研究概览
简要总结
This study will be an open-label, 12-week trial of risperidone in subjects with Asperger's Disorder, according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Criteria. The study has two arms, one involving pre- and post-treatment MRS studies, and one without MRS. The MRS arm will study 18-20 subjects ages 6 and above, with a target of 14 completing patients. For both arms, we plan to a enroll at total of 30 patients to achieve completion for 24 patients. The non-MRS arm of the study will include subjects 6-18 years of age, the bulk of which have completed the study as of the writing of this updated revision. Our hypotheses are that treatment of Asperger's patients with a low dose of risperidone will:
- decrease ratios of N-acetylaspartate (NAA), creatine, phosphocreatine (Cr + PCr), and choline in the prefrontal lobe, and
- decrease the severity of negative symptoms and overall improve social behavior, and
- that the two will be correlated.
Specific Aims
The primary objectives of this trial are to:
- Further assess and investigate the utility of risperidone in the treatment Asperger's disorder.
- Assess the efficacy of risperidone in normalizing increased frontal lobe metabolites.
- Assess the efficacy of risperidone in normalizing symptoms in Asperger's disorder patients using standardized rating scales to assess the impact on negative symptoms and on social interaction.
- Determine whether risperidone's effect on clinical improvement of Asperger's disorder, i.e., negative symptoms, is correlated with normalization of frontal lobe metabolites
- Accrue safety and tolerability data on risperidone for this population of patients.
This information could potentially be used to provide pilot data for a double blind trial
详细描述
STUDY DESIGN
This study will be an open-label, 12-week trial of risperidone in subjects with Asperger's Disorder, according to DSM-IV Criteria. The study has two arms, one involving pre- and post-treatment MRS studies, and one without MRS. The MRS arm will study 18-20 subjects ages 6 and above, with a target of 14 completing patients. For both arms, we plan to a enroll at total of 30 patients to achieve completion for 24 patients. The non-MRS arm of the study will include subjects 6-18 years of age, the bulk of which have completed the study as of the writing of this updated revision.
Subjects will first undergo a screening visit during which safety and diagnostic assessments are completed, and a minimum of 3 days will be allowed to evaluate the screening results. Then, the subjects will complete one or two practice sessions to provide training to achieve the necessary stillness for a duration that is sufficient to complete a MRS session. Upon completion of successful practice sessions, subjects will then be scheduled for a MRS visit. Once the MRS is successfully completed, subjects will be assigned to receive risperidone 0.25 mg at their baseline visit.
Response to risperidone will be measured at weeks 3, 6, 9, and 12 by the Scale for Assessment of Negative Symptoms (SANS). Additional secondary outcome measures are shown below (figure 1). A post-treatment MRS will be conducted after the Week 12 or early termination visit. Subjects will be given adequate medication supply to cover through the day of the final MRS visit.
Study Medication. Because Asperger's Disorder is diagnosed in childhood and is considered a childhood disease, our previous phase of the study focused on subjects ages 6 - 18. Published dosages of risperidone used in child, adolescent, and adult studies ranges from 0.25 to 11 mg per day. Most studies in children and adolescents begin with a starting dose of 0.25 mg bid, which is also appropriate for adults, and will be the starting dose planned for this study. The study progresses from a fixed to a titrated dose paradigm. After Week 6, dose will be increased (based on response and tolerability), ranging from one to two tablets twice daily (either 1 or 2 mg of risperidone daily). Again at Week 9, dose will be increased (based on response and tolerability), ranging from 1 mg to 4 mg per day of risperidone, one to four tablets twice a day of risperidone. Patients who have any trouble tolerating the starting dose may have their dose reduced to 0.25 mg per day and continue in the study. Patients who cannot tolerate the 0.25 mg dosage would discontinue the study in order to receive alternative treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be age 6 -18 for the Non-MRS arm of the study, and age 6 or above for the MRS arm of the study.
- •If applicable, a parent or legal guardian or legal representatives of study subject must provide informed consent and sign an informed consent document.
- •Female patients of childbearing age must be either postmenopausal for at least one year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral or parenteral hormonal contraceptives, intrauterine device; barrier and spermicide. Abstinence is not an acceptable method).
- •Female patients of child-bearing potential must have a negative pregnancy test to be performed at screening and baseline.
- •Patients must meet DSM-IV criteria for Asperger's Disorder. Other Axis I & II disorders excluded are listed below.
- •Patient must not have other serious, unstable illnesses and must be otherwise physically healthy on the basis of a physical examination, medical history, electrocardiogram and the results of blood biochemistry, hematology tests and a urinalysis.
- •Patient must have a negative urine drug screen with the exception of amphetamines if the patient is being treated with stimulants for four months or longer prior to entry.
排除标准
- •Patients who meet DSM-IV criteria for any psychotic disorder including schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder,psychotic disorder not otherwise specified, major depression with psychotic features, or bipolar disorder.
- •Patients who meet DSM-IV criteria for schizoid, schizotypal, or paranoid personality disorder. Patients who meet DSM-IV criteria for autistic disorder or pervasive developmental disorder.
- •Claustrophobic patients and those otherwise unable to successfully complete the MRS procedure prior to baseline.
- •Patients who meet criteria for substance abuse or dependence within the past three months. (Nicotine and caffeine are exceptions).
- •Patients believed by the investigator to be at significant risk for suicidal or violent behavior during the course of the trial.
- •Female patients who are pregnant or nursing.
- •Patients with a known or suspected seizure disorder.
- •If the results of the serum alanine transaminase (ALT) or aspartate aminotransferase (AST) are more than twice the upper limit of the central laboratory's reference range, the patient may not be enrolled. If the results of any other biochemistry, hematology or urinalysis tests are not within the central laboratory's reference ranges, the patient can be enrolled only on condition that the investigator judges that the deviations are not clinically significant. This should be clearly recorded on the laboratory report and in the source documents.
- •Patients with a history of neuroleptic malignant syndrome (NMS) or similar encephalopathic syndrome.
- •Patients who, by history, have received treatment with Risperdal or another neuroleptic (including olanzapine or quetiapine) within three months of baseline evaluation. Patients who have received a depot antipsychotic within one treatment cycle prior to screening. Patients who have taken an antidepressant, or lithium within 4 weeks of the trial, 6 weeks for fluoxetine. Patients who have taken any psychotropic medication within 1 week of the trial. Patients who require concomitant medications during the trial.
- •Patients with a suspected history of hypersensitivity or intolerance to risperidone.
- •Patients with a known or suspected history of severe drug allergy or hypersensitivity (e.g., Steven Johnson's syndrome)
- •Patients with an anticipated life expectancy of six months or less.
研究组 & 干预措施
Magnetic Resonance Spectroscopy
Subjects will receive a baseline MRS prior to and within 7 day of completing 12 weeks of standard treatment with.
干预措施: Risperidone (Drug)
Magnetic Resonance Spectroscopy
Subjects will receive a baseline MRS prior to and within 7 day of completing 12 weeks of standard treatment with.
干预措施: Magnetic Resonance Spectroscopy (Other)
NO-MRS
Subjects will receive 12 weeks of standard treatment of risperidone 0.25 to 11 mg per day, or early termination. Dose titration will based on response and tolerability.
干预措施: Risperidone (Drug)
结局指标
主要结局
Chang in the Scale for the Assessment of Negative Symptoms (SANS)
时间窗: Baseline, Week 3, 6, 9, 12 and up to 7 weeks post treatment
次要结局
- Change in Positive and Negative Symptom Scale (PANNS)(Baseline, Week 3, 6, 9, 12 and up to 7 weeks post treatment)
- Change in Brief Psychiatric Rating Scale (BPRS)(Baseline, Week 3, 6, 9, 12 and up to 7 weeks post treatment)
- Change in Montgomery Asberg Rating Scale (MADRS)(Baseline, Week 3, 6, 9, 12 and up to 7 weeks post treatment)
- Change in Global Assessment Scale (GAS)(Baseline, Week 3, 6, 9, 12 and up to 7 weeks post treatment)
- Change in Abnormal Involuntary Movement Scale (AIMS)(Baseline, Week 3, 6, 9, 12 and up to 7 weeks post treatment)
- Change in Neurocognitive test battery(Baseline, 12 weeks)
研究者
Donna Londino
Associate Professor
Augusta University