Ignite Creation Date:
2024-05-06 @ 4:03 AM
Last Modification Date:
2024-10-26 @ 11:43 AM
Study NCT ID:
NCT02446886
Status:
TERMINATED
Last Update Posted:
2021-01-22
First Post:
2015-05-07
Brief Title:
Adrenocorticotropic Hormone ACTH Effects on Myelination in Subjects With MS
Sponsor:
Weill Medical College of Cornell University
Organization:
Weill Medical College of Cornell University
Study Overview
Official Title:
Adrenocorticotropic Hormone ACTH Effects on Myelination in Subjects With MS
Status:
TERMINATED
Status Verified Date:
2020-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Slow enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary objective of this study is to determine if monthly pulse doses of a three-day course ACTH HP Acthar is more effective at recovering myelin at 12 months as measured by myelin water fraction MWF in new multiple sclerosis lesions as compared to one course of treatment
The main secondary objective is to utilize every three month MWF measurements to determine the peak time of remyelination in new multiple sclerosis lesions when followed over the course of 12 months
The main secondary objective is to utilize every three month MWF measurements to determine the peak time of remyelination in new multiple sclerosis lesions when followed over the course of 12 months
Detailed Description:
This pilot study proposal is designed to perform a chronological measurement of MWF in new contrast-enhancing lesions in subjects treated with ACTH during an acute exacerbation of MS
The initial course of ACTH HP Acthar will be administered as recommended in the package insert a subcutaneous daily dose of 80-120mg units daily for 2-3 weeks However as recommended in the package insert the dosage may be individualized according to the medical condition of each subject Therefore the frequency and dose of the drug may be determined by considering the severity of the disease and the initial response of the subject The typical dosing for an MS exacerbation is 80mgday for 3-5 days and it is expected that this will be the initial dosing for the majority of thesubjects
MS subjects enrolled in this study will be randomized into
One Time Treatment 80mgday ACTH for 3-5 days The dose could be adjusted based on the individual needs of the subjects up to 80-120mg units daily for 2-3 weeks
Monthly Treatments 80mgday ACTH for 3-5 days The dose could be adjusted based on the individual needs of the the subjects up to 80-120mg units daily for 2-3 weeks followed by monthly 80 mgday ACTH for 3 days for up to 12 months of treatment
The Judith Jaffe Multiple Sclerosis Center currently has over 1000 subjects in a clinical and MRI database The subjects who have signed consent for the database will have their standard of care MRI scans monitored for new enhancing lesions this will only have to be repeated if initial scan is not completed at our MS center with our current clinical protocol All RRMS subjects with new enhancing lesions will be considered for the study and approached regarding participation subjects that are considered candidates and consent for the study subjects will then be randomized 11 to receive one course of ACTH followed by monthly pulses vs receiving only one course of ACTH treatment All subjects will have follow-up MRIs are 3 months 6 months and 12 months post lesion onset for a total of 3 additional scans If a patient is identified as having an enhancing lesion from MRI scan not obtained through our database an additional scan will be obtained through the study and serve as the baseline MRI All subjects will receive the first course of ACTH within 4 weeks of new lesion detection
Multiple sclerosis MS is a very dynamic disease both biologically and clinically which is characterized by a temporally complex pattern of inflammation demyelinationremyelination and axonal loss The cycle of demyelination and remyelination has been shown to occur in MS lesions 12 High dose corticosteroids have been a mainstay of treatment for MS relapses Corticosteroid treatment shortens time to recovery from relapses presumably at least in part due to their anti-inflammatory effects Despite their anti-inflammatory properties corticosteroids have been shown to impair and delay remyelination in animal models of MS 34 and there is little clinical evidence of a longer-term beneficial effect Adrenocorticotropic hormone ACTH gel a long-acting formulation of the full sequence ACTH that includes other pro-opiomelanocortin POMC peptides is considered an alternative to corticosteroids in the treatment of relapses currently FDA approved for this indication ACTH gel exerts direct anti-inflammatory and immune-modulating effects within the central nervous system CNS These effects are mediated not only via induction of endogenous corticosteroid production but also via effects on melanocortin receptors 5 Studies have shown that ACTH and other melanocortins may reduce neuroinflammatory responses 6 and ACTH has been shown to protect mature oligodendrocytes from inflammation-related damage and excitotoxicity 7 Currently however there is a paucity of studies using more advanced MRI metrics to determine if ACTH may have reparative and neuroprotective properties in subjects with MS We propose to study monthly courses of ACTH in subjects with new lesions and compared to the one-time treatment course of ACTH for new activity We hypothesize that continued exposure to the anti-inflammatory effects of ACTH on new lesions would be superior to promoting remyelination as compared to a one-time treatment course Given that the majority of endogenous remyelination is felt to begin within months after lesion development and likely to be most prominent in the few months following a one year study is most likely sufficient to measure this process
T2 relaxometry is a MR imaging technique in which a series of T2-weighted images at different echo times are obtained and the contribution of water associated with myelin and other tissue compartments can be differentiated using T2 decay curve analysis8 The relative contribution of the myelin water represented as the myelin water fraction MWF has been shown to highly correlate with histological myelin measurement in animal models 9 and ex-vivo brain 1011 and has been applied to MS the subjects 12 The histological correlation of T2 relaxometry with myelin content makes it an excellent candidate as a biomarker for myelin content and it has been found to be reproducible and sensitive marker to change over time 13-16 Through the application a multi-slice 2D T2prep spiral gradient echo GRE imaging T2 data can be efficiently acquired 1718 and we have further optimized a 3D T2prep GRE sequence at 3T for which full brain coverage can be achieved within 10 minutes 19 One of the main advantages of using T2 relaxometry and MWF as a surrogate for myelin over other advanced MR modalities lies in the T2 spectrum the T2 decay curve analysis Both MWF and the extracellular T2 component the intermediate peak within the T2 spectrum can increase with edema 20 thus once the extracellular pool stabilizes we can ensure that any change in MWF is a true reflection of myelination
The primary objective of this study is to determine if monthly pulse doses of a three-day course ACTH HP Acthar is more effective at recovering myelin at 12 months as measured by MWF in new multiple sclerosis lesions as compared to one course of treatment
The main secondary objective is to utilize every three-month MWF measurements to determine the peak time of remyelination in new multiple sclerosis lesions when followed over the course of 12 months
The initial course of ACTH HP Acthar will be administered as recommended in the package insert a subcutaneous daily dose of 80-120mg units daily for 2-3 weeks However as recommended in the package insert the dosage may be individualized according to the medical condition of each subject Therefore the frequency and dose of the drug may be determined by considering the severity of the disease and the initial response of the subject The typical dosing for an MS exacerbation is 80mgday for 3-5 days and it is expected that this will be the initial dosing for the majority of thesubjects
MS subjects enrolled in this study will be randomized into
One Time Treatment 80mgday ACTH for 3-5 days The dose could be adjusted based on the individual needs of the subjects up to 80-120mg units daily for 2-3 weeks
Monthly Treatments 80mgday ACTH for 3-5 days The dose could be adjusted based on the individual needs of the the subjects up to 80-120mg units daily for 2-3 weeks followed by monthly 80 mgday ACTH for 3 days for up to 12 months of treatment
The Judith Jaffe Multiple Sclerosis Center currently has over 1000 subjects in a clinical and MRI database The subjects who have signed consent for the database will have their standard of care MRI scans monitored for new enhancing lesions this will only have to be repeated if initial scan is not completed at our MS center with our current clinical protocol All RRMS subjects with new enhancing lesions will be considered for the study and approached regarding participation subjects that are considered candidates and consent for the study subjects will then be randomized 11 to receive one course of ACTH followed by monthly pulses vs receiving only one course of ACTH treatment All subjects will have follow-up MRIs are 3 months 6 months and 12 months post lesion onset for a total of 3 additional scans If a patient is identified as having an enhancing lesion from MRI scan not obtained through our database an additional scan will be obtained through the study and serve as the baseline MRI All subjects will receive the first course of ACTH within 4 weeks of new lesion detection
Multiple sclerosis MS is a very dynamic disease both biologically and clinically which is characterized by a temporally complex pattern of inflammation demyelinationremyelination and axonal loss The cycle of demyelination and remyelination has been shown to occur in MS lesions 12 High dose corticosteroids have been a mainstay of treatment for MS relapses Corticosteroid treatment shortens time to recovery from relapses presumably at least in part due to their anti-inflammatory effects Despite their anti-inflammatory properties corticosteroids have been shown to impair and delay remyelination in animal models of MS 34 and there is little clinical evidence of a longer-term beneficial effect Adrenocorticotropic hormone ACTH gel a long-acting formulation of the full sequence ACTH that includes other pro-opiomelanocortin POMC peptides is considered an alternative to corticosteroids in the treatment of relapses currently FDA approved for this indication ACTH gel exerts direct anti-inflammatory and immune-modulating effects within the central nervous system CNS These effects are mediated not only via induction of endogenous corticosteroid production but also via effects on melanocortin receptors 5 Studies have shown that ACTH and other melanocortins may reduce neuroinflammatory responses 6 and ACTH has been shown to protect mature oligodendrocytes from inflammation-related damage and excitotoxicity 7 Currently however there is a paucity of studies using more advanced MRI metrics to determine if ACTH may have reparative and neuroprotective properties in subjects with MS We propose to study monthly courses of ACTH in subjects with new lesions and compared to the one-time treatment course of ACTH for new activity We hypothesize that continued exposure to the anti-inflammatory effects of ACTH on new lesions would be superior to promoting remyelination as compared to a one-time treatment course Given that the majority of endogenous remyelination is felt to begin within months after lesion development and likely to be most prominent in the few months following a one year study is most likely sufficient to measure this process
T2 relaxometry is a MR imaging technique in which a series of T2-weighted images at different echo times are obtained and the contribution of water associated with myelin and other tissue compartments can be differentiated using T2 decay curve analysis8 The relative contribution of the myelin water represented as the myelin water fraction MWF has been shown to highly correlate with histological myelin measurement in animal models 9 and ex-vivo brain 1011 and has been applied to MS the subjects 12 The histological correlation of T2 relaxometry with myelin content makes it an excellent candidate as a biomarker for myelin content and it has been found to be reproducible and sensitive marker to change over time 13-16 Through the application a multi-slice 2D T2prep spiral gradient echo GRE imaging T2 data can be efficiently acquired 1718 and we have further optimized a 3D T2prep GRE sequence at 3T for which full brain coverage can be achieved within 10 minutes 19 One of the main advantages of using T2 relaxometry and MWF as a surrogate for myelin over other advanced MR modalities lies in the T2 spectrum the T2 decay curve analysis Both MWF and the extracellular T2 component the intermediate peak within the T2 spectrum can increase with edema 20 thus once the extracellular pool stabilizes we can ensure that any change in MWF is a true reflection of myelination
The primary objective of this study is to determine if monthly pulse doses of a three-day course ACTH HP Acthar is more effective at recovering myelin at 12 months as measured by MWF in new multiple sclerosis lesions as compared to one course of treatment
The main secondary objective is to utilize every three-month MWF measurements to determine the peak time of remyelination in new multiple sclerosis lesions when followed over the course of 12 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None