Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06537700
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-17
Brief Title:
OnaBotulinumtoxin-A in Chronic Migraine Patients with Short or Long Disease History the BACH Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
OnaBotulinumtoxin-A Effectiveness Evaluation in Chronic Migraine Patients with Short or Long Disease History an Italian Multicentric Study the BACH Study
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BACH
Brief Summary:
The goal of this observational prospective multicentric study 12 months duration is to investigate whether the history of Chronic Migraine and more precisely its duration for over or less than 10 years can predict OBT-A treatment effectiveness
Since CM patients may have a complex psychopathological profile and psychiatric symptoms represent a bad prognostic factor influencing treatment effectiveness the present study will also aim at evaluating if the psychopathological profile of the enrolled patients may influence the outcome
Since CM patients may have a complex psychopathological profile and psychiatric symptoms represent a bad prognostic factor influencing treatment effectiveness the present study will also aim at evaluating if the psychopathological profile of the enrolled patients may influence the outcome
Detailed Description:
Onabotulinumtoxin-A OBT-A is a worldwide approved preventive treatment for patients suffering from Chronic Migraine CM 13 ICHD III 2018 Its effectiveness in reducing headache frequency and disability has been demonstrated by two well-designed phase III clinical trials PREEMPT 1 and 2 and more recently by some real-life studies
However the use of OBT-A in the real world clinical practice has been still raising some issues ie searching for more adequate patients selection when discontinuing the OBT-A treatment and when resuming it finding associated patients psychopathological profile possibly influencing the treatment and so on Moreover finding some indicators of good or bad prognosis coming from OBT-A real-life experience could be of help for the clinicians to individuate the best candidates to the treatment
The aim of the present study is mainly to investigate whether the history of Chronic Migraine and more precisely its duration for over or less than 10 years can predict OBT-A treatment effectiveness In other words the study will aim to establish whether starting OBT-A treatment earlier in CM patients life could make it more effective
Since psychiatric symptoms may represent prognostic factors influencing treatment effectiveness the present study will also aim at evaluating if the psychopathological profile of the enrolled patients may influence the outcome
Consecutive CM patients treated in Italian tertiary level Headache Centers and classified according to CM history shorterlonger than 10 years will be enrolled
Aims
To compare OBT-A treatment effectiveness in patients with shorter 1-9 yrs and longer 10 or longer years history of CM in terms of
monthly migraine MMD or headache MHD days
monthly acute medications MAM
disability scales Headache Impact Test HIT-6 Migraine Disability Assessment MIDAS questionnaire scores
pain intensity and quality
Objectives
to investigate whether the history of Chronic Migraine over or less than 10 years can predict OBT-A treatment effectiveness
to find possible indicators of good or bad prognosis coming among psychiatric comorbidities of the enrolled patients
Consecutive CM patients according to ICHD-3 13 treated in Italian headache centers undergoing OBT-A will be enrolled
Methods All patients will fill a headache diary to report MMDs and acute medications taken every month
Disability will be assessed by means of HIT-6 and MIDAS Moreover the intensity and quality of perceived pain will be evaluated by means of Numerical Rating Scale NRS 11-point Box Scale BS-11 Present Pain Intensity PPI Behavioral Rating Scale BRS-6 e Short-form McGill Pain Questionnaire SF-MPQ
The psychopathological profile will be evaluated at different times of the study by means of the following psychological questionnaires Beck Depression Inventory BDI-II State-Trait Anxiety Inventory STAI-Y Toronto Alexithymia Scale TAS-20
At enrolment T0 before starting the treatment patients will have to fill a questionnaire about the previous 3 months screening phase including
MMD and MHD
MAM
NRS BS-11 PPI BRS-6 e SF-MPQ scales
MIDAS e HIT-6 scale
BDI-II STAI-Y TAS-20 questionnaires After completing the diary and scales above patients will receive OBT-A treatment according to PREEMPT protocol
Patients will be divided into 2 groups according to their CM history duration A those from 1 to 9 years and B those with 10 or more years of CM history
Patients will be re-evaluated every 3 months at each OBT-A cycle during the whole year of treatment At every evaluation time patients will show their diary of headaches with MMD and MAM taken
At T3 and T9 3 and 9 months respectively after T0 patients will fill the questionnaire including MMD and MAM taken in the previous 3 months pain evaluation scales MIDAS e HIT-6 scales
At T6 and T12 6 and 12 months respectively from T0 T12 being the final evaluation patients will have to fill all questionnairesscales as at T0
Outcomes Primary endpoint Change in the mean number of MMD or MHD from baseline to months 6 through 12 between groups
Secondary
1 50 or greater reduction in MMD from baseline to months 6 through 12 between groups
2 change in the number of MAM from baseline to months 6 through 12 between groups
3 change in pain intensity and quality scores from baseline to months 6 through 12 between groups
4 change in terms of psychological profile STAI-Y TAS-20 scales in the stratified subgroups based on Z score of BDI-II scale 0 18 between groups
Statistical analysis The data will be collected in an electronic database in anonymous form that will be protected by a password for each participant center
On the basis of primary outcome change during the follow-up vs baseline of MMD a general linear model with mixed effects will be applied which will allow to evaluate considering the within-subject dependencies and allowing to use all the observations available for each subject even if for example the measurement of a subject at the time Tx should be missing the interaction time X group and estimate if and when during follow-up a significant difference between the two groups will occur According to a previous study Vernieri et al Headache 2019 the distribution of MMD is expected to follow a Gaussian distribution therefore the general linear model will be a mixed-effects ANOVA For some of the other variables such as the number of analgesics or MIDAS a generalized model will be applied to take into account the non-Gaussian nature of their distributions
The sample size has been predefined according to the primary outcome with the following approach Thanks to the previous study Vernieri et al 2019 it was possible to estimate the standard deviations SD of the changes of MMD between baselines and subsequent times The maximum standard deviation was observed between baseline T0 and T4 1 year and was 8 with very similar values in two independent centers 78 and 82 Since this SD was estimated on 100 patients the 95 confidence interval for SD is 70-93 In order to avoid underestimation of the variability of the primary outcome we have therefore set SD equal to the upper limit of the confidence interval built on the maximum SD found of the variations vs baseline during the follow-up and that is SD93
In the following table it is reported the sample size required to have a power of 90 to recognize as statistically significant at two-tails alpha level set at 005 the differences between the expected decreases specified in the first two columns Since the evaluation times at follow-up will be 4 T3 T6 T9 T12 the probability of error of type I has been divided by 4 in order to keep the overall alpha error below 5
In the cited study a decrease after 6 months of treatment and confirmed at 12 months of about 7 days of migrainemonth was observed This absolute decrease corresponded to a percentage change of about 30-35 The hypothesis is that chronic patients from more than 10 years may benefit less from treatment and in particular that between the two groups there is a difference in efficacy of 4 hypothesis 1 and 6 hypothesis 2 daysmonth
Hypothesis 1 Expected pre-post decrease Group1 10y 5 SD93 Expected pre-post decrease Group1 10y 9 SD93 Power 1-b 90 a two-tails 00125 N Group1 115 N Group1 115
Hypothesis 2 Expected pre-post decrease Group1 10y 4 SD93 Expected pre-post decrease Group1 10y 10 SD93 Power 1-b 90 a two-tails 00125 N Group1 52 N Group1 52
With these numbers it is also possible to calculate that there will be a probability of 90 to recognize as statistically significant at alpha level 005 standardized effect size f008 hypothesis1 and f012 hypothesis 2 for the interaction Time X Group The calculation for the interaction was based on an ANOVA with 4 repeated measurements after T0 T3 T6 T9 T12 assuming the same correlation between the baseline follow-up assessments observed in the study by Vernieri et al 2019 and applying a correction for lack of sphericity epsilon09 Considering that f010 is conventionally classifiable as small the indicated number of values therefore allow to be sensitive to small variations even if clinically relevant
Reference
Vernieri et al Onabotulinumtoxin-A in Chronic Migraine Should Timing and Definition of Non-Responder Status Be Revised Suggestions From a Real-Life Italian Multicenter Experience Headache 2019 Sep5981300-1309
However the use of OBT-A in the real world clinical practice has been still raising some issues ie searching for more adequate patients selection when discontinuing the OBT-A treatment and when resuming it finding associated patients psychopathological profile possibly influencing the treatment and so on Moreover finding some indicators of good or bad prognosis coming from OBT-A real-life experience could be of help for the clinicians to individuate the best candidates to the treatment
The aim of the present study is mainly to investigate whether the history of Chronic Migraine and more precisely its duration for over or less than 10 years can predict OBT-A treatment effectiveness In other words the study will aim to establish whether starting OBT-A treatment earlier in CM patients life could make it more effective
Since psychiatric symptoms may represent prognostic factors influencing treatment effectiveness the present study will also aim at evaluating if the psychopathological profile of the enrolled patients may influence the outcome
Consecutive CM patients treated in Italian tertiary level Headache Centers and classified according to CM history shorterlonger than 10 years will be enrolled
Aims
To compare OBT-A treatment effectiveness in patients with shorter 1-9 yrs and longer 10 or longer years history of CM in terms of
monthly migraine MMD or headache MHD days
monthly acute medications MAM
disability scales Headache Impact Test HIT-6 Migraine Disability Assessment MIDAS questionnaire scores
pain intensity and quality
Objectives
to investigate whether the history of Chronic Migraine over or less than 10 years can predict OBT-A treatment effectiveness
to find possible indicators of good or bad prognosis coming among psychiatric comorbidities of the enrolled patients
Consecutive CM patients according to ICHD-3 13 treated in Italian headache centers undergoing OBT-A will be enrolled
Methods All patients will fill a headache diary to report MMDs and acute medications taken every month
Disability will be assessed by means of HIT-6 and MIDAS Moreover the intensity and quality of perceived pain will be evaluated by means of Numerical Rating Scale NRS 11-point Box Scale BS-11 Present Pain Intensity PPI Behavioral Rating Scale BRS-6 e Short-form McGill Pain Questionnaire SF-MPQ
The psychopathological profile will be evaluated at different times of the study by means of the following psychological questionnaires Beck Depression Inventory BDI-II State-Trait Anxiety Inventory STAI-Y Toronto Alexithymia Scale TAS-20
At enrolment T0 before starting the treatment patients will have to fill a questionnaire about the previous 3 months screening phase including
MMD and MHD
MAM
NRS BS-11 PPI BRS-6 e SF-MPQ scales
MIDAS e HIT-6 scale
BDI-II STAI-Y TAS-20 questionnaires After completing the diary and scales above patients will receive OBT-A treatment according to PREEMPT protocol
Patients will be divided into 2 groups according to their CM history duration A those from 1 to 9 years and B those with 10 or more years of CM history
Patients will be re-evaluated every 3 months at each OBT-A cycle during the whole year of treatment At every evaluation time patients will show their diary of headaches with MMD and MAM taken
At T3 and T9 3 and 9 months respectively after T0 patients will fill the questionnaire including MMD and MAM taken in the previous 3 months pain evaluation scales MIDAS e HIT-6 scales
At T6 and T12 6 and 12 months respectively from T0 T12 being the final evaluation patients will have to fill all questionnairesscales as at T0
Outcomes Primary endpoint Change in the mean number of MMD or MHD from baseline to months 6 through 12 between groups
Secondary
1 50 or greater reduction in MMD from baseline to months 6 through 12 between groups
2 change in the number of MAM from baseline to months 6 through 12 between groups
3 change in pain intensity and quality scores from baseline to months 6 through 12 between groups
4 change in terms of psychological profile STAI-Y TAS-20 scales in the stratified subgroups based on Z score of BDI-II scale 0 18 between groups
Statistical analysis The data will be collected in an electronic database in anonymous form that will be protected by a password for each participant center
On the basis of primary outcome change during the follow-up vs baseline of MMD a general linear model with mixed effects will be applied which will allow to evaluate considering the within-subject dependencies and allowing to use all the observations available for each subject even if for example the measurement of a subject at the time Tx should be missing the interaction time X group and estimate if and when during follow-up a significant difference between the two groups will occur According to a previous study Vernieri et al Headache 2019 the distribution of MMD is expected to follow a Gaussian distribution therefore the general linear model will be a mixed-effects ANOVA For some of the other variables such as the number of analgesics or MIDAS a generalized model will be applied to take into account the non-Gaussian nature of their distributions
The sample size has been predefined according to the primary outcome with the following approach Thanks to the previous study Vernieri et al 2019 it was possible to estimate the standard deviations SD of the changes of MMD between baselines and subsequent times The maximum standard deviation was observed between baseline T0 and T4 1 year and was 8 with very similar values in two independent centers 78 and 82 Since this SD was estimated on 100 patients the 95 confidence interval for SD is 70-93 In order to avoid underestimation of the variability of the primary outcome we have therefore set SD equal to the upper limit of the confidence interval built on the maximum SD found of the variations vs baseline during the follow-up and that is SD93
In the following table it is reported the sample size required to have a power of 90 to recognize as statistically significant at two-tails alpha level set at 005 the differences between the expected decreases specified in the first two columns Since the evaluation times at follow-up will be 4 T3 T6 T9 T12 the probability of error of type I has been divided by 4 in order to keep the overall alpha error below 5
In the cited study a decrease after 6 months of treatment and confirmed at 12 months of about 7 days of migrainemonth was observed This absolute decrease corresponded to a percentage change of about 30-35 The hypothesis is that chronic patients from more than 10 years may benefit less from treatment and in particular that between the two groups there is a difference in efficacy of 4 hypothesis 1 and 6 hypothesis 2 daysmonth
Hypothesis 1 Expected pre-post decrease Group1 10y 5 SD93 Expected pre-post decrease Group1 10y 9 SD93 Power 1-b 90 a two-tails 00125 N Group1 115 N Group1 115
Hypothesis 2 Expected pre-post decrease Group1 10y 4 SD93 Expected pre-post decrease Group1 10y 10 SD93 Power 1-b 90 a two-tails 00125 N Group1 52 N Group1 52
With these numbers it is also possible to calculate that there will be a probability of 90 to recognize as statistically significant at alpha level 005 standardized effect size f008 hypothesis1 and f012 hypothesis 2 for the interaction Time X Group The calculation for the interaction was based on an ANOVA with 4 repeated measurements after T0 T3 T6 T9 T12 assuming the same correlation between the baseline follow-up assessments observed in the study by Vernieri et al 2019 and applying a correction for lack of sphericity epsilon09 Considering that f010 is conventionally classifiable as small the indicated number of values therefore allow to be sensitive to small variations even if clinically relevant
Reference
Vernieri et al Onabotulinumtoxin-A in Chronic Migraine Should Timing and Definition of Non-Responder Status Be Revised Suggestions From a Real-Life Italian Multicenter Experience Headache 2019 Sep5981300-1309
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