Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00352196
Status:
COMPLETED
Last Update Posted:
2015-01-14
First Post:
2006-07-12
Brief Title:
Janssen Aspergers MRS Magnetic Resonance Spectroscopy Risperidone Study
Sponsor:
Augusta University
Organization:
Augusta University
Study Overview
Official Title:
A Biological Basis of Therapy for Negative Symptom Spectrum Disorders Risperdal Effect on Frontal Metabolism in Aspergers Disorder
Status:
COMPLETED
Status Verified Date:
2015-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will be an open-label 12-week trial of risperidone in subjects with Aspergers 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 Aspergers patients with a low dose of risperidone will
1 decrease ratios of N-acetylaspartate NAA creatine phosphocreatine Cr PCr and choline in the prefrontal lobe and
2 decrease the severity of negative symptoms and overall improve social behavior and
3 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 Aspergers disorder
Assess the efficacy of risperidone in normalizing increased frontal lobe metabolites
Assess the efficacy of risperidone in normalizing symptoms in Aspergers disorder patients using standardized rating scales to assess the impact on negative symptoms and on social interaction
Determine whether risperidones effect on clinical improvement of Aspergers disorder ie 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
1 decrease ratios of N-acetylaspartate NAA creatine phosphocreatine Cr PCr and choline in the prefrontal lobe and
2 decrease the severity of negative symptoms and overall improve social behavior and
3 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 Aspergers disorder
Assess the efficacy of risperidone in normalizing increased frontal lobe metabolites
Assess the efficacy of risperidone in normalizing symptoms in Aspergers disorder patients using standardized rating scales to assess the impact on negative symptoms and on social interaction
Determine whether risperidones effect on clinical improvement of Aspergers disorder ie 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
Detailed Description:
STUDY DESIGN
This study will be an open-label 12-week trial of risperidone in subjects with Aspergers 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 025 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 Aspergers 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 025 to 11 mg per day Most studies in children and adolescents begin with a starting dose of 025 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 025 mg per day and continue in the study Patients who cannot tolerate the 025 mg dosage would discontinue the study in order to receive alternative treatment
Schedule of Events and Observations
Screening Visit A Structured Clinical Interview for Diagnosis SCID in conjunction with DSM-IV criteria and a psychiatric history will allow the study physicians to establish and confirm a diagnosis of Aspergers disorder Medical history vital signs clinical labs chemistry complete blood count CBC thyroid function urinalysis urine drug screen and blood pregnancy test fecund females only a physical exam and an EKG will be performed to determine patient safety
Blood Draws Additional lab samples will be collected at both screening and end of study to explore 1 the effects of diet on treatment outcomes with risperidone and 2 effects of risperidone treatment on levels of Brain Derived Neurotrophic Factor BDNF and Nerve Growth Factor NGF The additional blood will amount to an approximate total of 8 tablespoons of blood collected during the study
MRS Visits and Practice Sessions Subjects enrolling in the MRS arm will be scheduled for a pretreatment MRS which will take place after the screening visit but before the baseline visit and prior to starting risperidone Subjects will also have a post-treatment MRS within 7 days of their week 12 visit or at study termination Patients will be supplied with enough medication to continue treatment until the MRS measures are complete
Subjects may be required based on the investigators discretion to complete one or two sessions during the screening period for Practice Sessions for MRS studies to better prepare subjects for the level of stillness needed for MRS studies The practice sessions will last approximately one hour and will be performed at the Medical College of Georgia MCG Office of Clinical Investigative Services located at 1521 Pope Ave Suite FF-100 Practice Sessions may also be performed at the MRI suite at MCG to allow the subject to see or lie in the MRI machine depending on availability
Rationale for practice sessions We have learned that these sessions may be necessary to help subjects achieve the stillness required for MRS During the sessions subjects will be trained to remain still while lying on a padded stretcher using behavioral and relaxation training techniques performed by a qualified investigator Other efforts will be made to simulate the MRS environment that may include playing recorded sounds of a MRI machine and simulation of the padded head supports
In most cases the Practice Sessions would be all done prior to the MRS visit but in some cases of a failed MRS visit the investigator may choose to schedule another practice session prior to re-trying the MRS visit The practice session will supplement the standard efforts used to support patients compliance during MRI procedures For example part of the hospitals usual care during MRI studies includes the option of having the patient wear video goggles and headphones Subjects in our study may view a calming video of neutral content to aid in problems affecting stillness
Behavioral reinforcement and subject payments during practice sessions Part of the payment for practice sessions will be used as a behavioral reinforcement plan and this will be in addition to the 20 payment for clinic visits reimbursement for travel over 25 miles one-way 28mile and 50 for the MRS visit paid regardless of success or failure
The additional subject payment in the practice session will be used as incentive and behavioral reinforcement for achieving stillness Specifically subjects will receive a token such as a poker chip or printed paper token worth 500 for each 5-minute period they remain still If a subjects head moves during a period they will be told they have to begin a new period The achievement of stillness will be determined by the investigator at the time taking into account the actual observed stillness and the need to encourage and reward the subjects efforts
The actual stillness practice will last up to 40 minutes and the subject will receive a token for each 5 minute period they remain still for up to 8 periods The total additional payment for behavioral reinforcement will range from 500 to 4000 to be paid in the same way as other subject payments In the case of adolescent subjects parents will be encouraged to consider the additional practice session payments to go to the child as a reward for the childs efforts
Baseline Visit Subjects will be scheduled for baseline procedures when lab results and MRS values are reviewed and approved by the study physician in most cases expected to be a period of 7 days This visit will consist of medical-psychiatric interviews and neurocognitive testing A urine pregnancy test done previously at screening may be repeated at baseline based on the judgement of the investigator
This study will be an open-label 12-week trial of risperidone in subjects with Aspergers 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 025 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 Aspergers 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 025 to 11 mg per day Most studies in children and adolescents begin with a starting dose of 025 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 025 mg per day and continue in the study Patients who cannot tolerate the 025 mg dosage would discontinue the study in order to receive alternative treatment
Schedule of Events and Observations
Screening Visit A Structured Clinical Interview for Diagnosis SCID in conjunction with DSM-IV criteria and a psychiatric history will allow the study physicians to establish and confirm a diagnosis of Aspergers disorder Medical history vital signs clinical labs chemistry complete blood count CBC thyroid function urinalysis urine drug screen and blood pregnancy test fecund females only a physical exam and an EKG will be performed to determine patient safety
Blood Draws Additional lab samples will be collected at both screening and end of study to explore 1 the effects of diet on treatment outcomes with risperidone and 2 effects of risperidone treatment on levels of Brain Derived Neurotrophic Factor BDNF and Nerve Growth Factor NGF The additional blood will amount to an approximate total of 8 tablespoons of blood collected during the study
MRS Visits and Practice Sessions Subjects enrolling in the MRS arm will be scheduled for a pretreatment MRS which will take place after the screening visit but before the baseline visit and prior to starting risperidone Subjects will also have a post-treatment MRS within 7 days of their week 12 visit or at study termination Patients will be supplied with enough medication to continue treatment until the MRS measures are complete
Subjects may be required based on the investigators discretion to complete one or two sessions during the screening period for Practice Sessions for MRS studies to better prepare subjects for the level of stillness needed for MRS studies The practice sessions will last approximately one hour and will be performed at the Medical College of Georgia MCG Office of Clinical Investigative Services located at 1521 Pope Ave Suite FF-100 Practice Sessions may also be performed at the MRI suite at MCG to allow the subject to see or lie in the MRI machine depending on availability
Rationale for practice sessions We have learned that these sessions may be necessary to help subjects achieve the stillness required for MRS During the sessions subjects will be trained to remain still while lying on a padded stretcher using behavioral and relaxation training techniques performed by a qualified investigator Other efforts will be made to simulate the MRS environment that may include playing recorded sounds of a MRI machine and simulation of the padded head supports
In most cases the Practice Sessions would be all done prior to the MRS visit but in some cases of a failed MRS visit the investigator may choose to schedule another practice session prior to re-trying the MRS visit The practice session will supplement the standard efforts used to support patients compliance during MRI procedures For example part of the hospitals usual care during MRI studies includes the option of having the patient wear video goggles and headphones Subjects in our study may view a calming video of neutral content to aid in problems affecting stillness
Behavioral reinforcement and subject payments during practice sessions Part of the payment for practice sessions will be used as a behavioral reinforcement plan and this will be in addition to the 20 payment for clinic visits reimbursement for travel over 25 miles one-way 28mile and 50 for the MRS visit paid regardless of success or failure
The additional subject payment in the practice session will be used as incentive and behavioral reinforcement for achieving stillness Specifically subjects will receive a token such as a poker chip or printed paper token worth 500 for each 5-minute period they remain still If a subjects head moves during a period they will be told they have to begin a new period The achievement of stillness will be determined by the investigator at the time taking into account the actual observed stillness and the need to encourage and reward the subjects efforts
The actual stillness practice will last up to 40 minutes and the subject will receive a token for each 5 minute period they remain still for up to 8 periods The total additional payment for behavioral reinforcement will range from 500 to 4000 to be paid in the same way as other subject payments In the case of adolescent subjects parents will be encouraged to consider the additional practice session payments to go to the child as a reward for the childs efforts
Baseline Visit Subjects will be scheduled for baseline procedures when lab results and MRS values are reviewed and approved by the study physician in most cases expected to be a period of 7 days This visit will consist of medical-psychiatric interviews and neurocognitive testing A urine pregnancy test done previously at screening may be repeated at baseline based on the judgement of the investigator
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MCG HAC File 01-09-063 | OTHER | Institutional Review Board | None |