Clinical trial NCT02290444
Conditions: Multiple Sclerosis
Keywords: Acute Relapsing Multiple Sclerosis Relapsing-Remitting Multiple Sclerosis Multiple Sclerosis, Chronic Progressive
Sponsor: State University of New York at Buffalo
Start date: 2013-08-01; Completion date: 2018-11-01
Enrollment: 64 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the effect of a medication called Acthar on recovery from multiple sclerosis-related relapses that impact cognition.

Detailed description:
This is a prospective, open-label study of Acthar administered as treatment for an acute cognitive relapse. Primary and secondary endpoints will be collected prior to Acthar administration and at 3-month follow-up. Comparison will be made to a stable MS control group.

The objectives of the study are:

1. To replicate prior findings with steroid therapy for MS patients for cognitive relapses, using instead Acthar Gel as the treating agent. The investigators will determine if the decrease on cognitive endpoints at the time of relapse exceeds that of stable MS controls.
2. To compare the effects above to a previously acquired dataset of relapsing patients treated with steroids. This is a quasi-experimental design in so far as the steroid treated group data were previously acquired in a separate study.

The primary hypothesis of the study is that, due to the enhanced melanocortin response in Acthar the recovery from cognitive changes occurring during cognitively focused relapse will be significant compared to stable MS patients matched on age, time since testing, and cognitive performance on the SDMT.

Target enrollment for the Acthar treatment group will be 30 MS patients under care at the Jacobs Neurological Institute with existing neuropsychological baseline in the past four years in whom a cognitive relapse or new supratentorial GAD enhancing lesion(s) on MRI have been identified. Cognitive relapse will be identified based on clinical presentation of acute worsening of cognitive symptoms in the domains of processing speed, concentration, episodic memory, working memory, and/or fatigue. Patients whose clinical MRI indicate new active GAD enhancing lesions will be screened for the presence of self-perceived cognitive decline, without new physical symptoms. Thirty (30) clinically stable MS patients matched on age, time since testing, and cognitive performance on the SDMT will be recruited from the pool of patients with existing cognitive baselines.

Arms: arm 1: For individuals experiencing cognitive relapses/exacerbations, 5ml/80 IU of Adrenocorticotropic Hormone will be administered through either subcutaneous or intramuscular self-injection (selected by the patient) for 5-days. arm 2: Individuals whose Multiple Sclerosis is currently in a stable state (not currently or recently exacerbating) are age-matched with relapsing MS patients. There is no intervention for individuals with MS whose are currently in a stable state.
Interventions: intervention 1: Adrenocorticotropic Hormone
Intervention descriptions: intervention 1: Acthar Gel will be administered in accordance with the recommendations set forth in the package insert. The dosage may be individualized according to the medical condition of each patient. Frequency and dose of the drug may be determined by considering the severity of the disease and the initial response of the patient.

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 46 
 
 
 
 
 
 
 
 
 
 
 
 
 
Effects of Acthar on Recovery From Cognitive Relapses in MS 
NCT02290444 
Study Protocol 
Document Revision Date: June 12, 2018 
IRB Approval of Revision: July 30, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 2 of 46 
Revised: July 12, 2017 
 
INSTRUCTIONS: Complete Research Protocol (HRP-503) 
 Depending on the nature of what you are doing, some sections may 
not be applicable to your research. If so, you must provide the 
reason why the section is not applicable for the response. For 
example, most behavioral studies would answer all questions in 
section 30 with words to the effect of “drugs and medical devices 
are not used in this study.” 
 When you write a protocol, keep an electronic copy. You will need 
to modify this copy when making changes. 
 Do not remove the italics instructions or headings. 
 If you are pasting information from other documents be sure to use 
the “Merge Formatting” paste option so that the formatting of the 
response boxes is not lost.  If information is presented outside of 
the response boxes, it will not be accepted. 
 If this study involves multiple participant groups who participate 
in different research procedures, consent processes, etc., be 
certain to provide information in each applicable section for each 
participant group and clearly label each participant group within 
a section or subsection.  
 
 
PROTOCOL TITLE: 
Include the full protocol title. 
Response: Effects of adrenocorticotropic hormone (Acthar gel®) on 
recovery from cognitive relapses in MS. 
 
PRINCIPAL INVESTIGATOR: 
Name 
Department 
Telephone Number 
Email Address 
Response:  
Ralph HB Benedict 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 3 of 46 
Revised: July 12, 2017 
Neurology 
716-323-0556 
Benedict@buffalo.edu 
VERSION NUMBER: 
Include the version number of this protocol. 
Response: 4 
 
DATE: 
Include the date of submission or revision. 
Response: June 12 2018  
 
Grant Applicability: 
Describe whether or not this protocol is funded by a grant or contract and if so, 
what portions of the grant this study covers. 
Response:  
This study is supported by Mallinckrodt Pharmaceuticals (formerly 
Questcor).  
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 4 of 46 
Revised: July 12, 2017 
Table of Contents 
1.0 
Objectives ................................................................................................................ 5 
2.0 
Background .............................................................................................................. 5 
3.0 
Inclusion and Exclusion Criteria ............................................................................ 11 
4.0 
Study-Wide Number of Subjects (Multisite/Multicenter Only) ............................ 13 
5.0 
Study-Wide Recruitment Methods (Multisite/Multicenter Only).......................... 13 
6.0 
Multi-Site Research (Multisite/Multicenter Only)................................................. 14 
7.0 
Study Timelines ..................................................................................................... 15 
8.0 
Study Endpoints ..................................................................................................... 15 
9.0 
Procedures Involved............................................................................................... 16 
10.0 Data and Specimen Banking .................................................................................. 22 
11.0 Data Management .................................................................................................. 22 
12.0 Provisions to Monitor the Data and Ensure the Safety of Subjects ....................... 25 
13.0 Withdrawal of Subjects .......................................................................................... 27 
14.0 Risks to Subjects .................................................................................................... 27 
15.0 Potential Benefits to Subjects ................................................................................ 30 
16.0 Vulnerable Populations .......................................................................................... 30 
17.0 Community-Based Participatory Research ............................................................ 31 
18.0 Sharing of Results with Subjects ........................................................................... 31 
19.0 Setting .................................................................................................................... 31 
20.0 Resources Available............................................................................................... 32 
21.0 Prior Approvals ...................................................................................................... 34 
22.0 Recruitment Methods ............................................................................................. 34 
23.0 Local Number of Subjects ..................................................................................... 35 
24.0 Confidentiality ....................................................................................................... 36 
25.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 37 
26.0 Compensation for Research-Related Injury ........................................................... 37 
27.0 Economic Burden to Subjects ................................................................................ 38 
28.0 Consent Process ..................................................................................................... 38 
29.0 Process to Document Consent in Writing .............................................................. 43 
30.0 Drugs or Devices.................................................................................................... 43 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 5 of 46 
Revised: July 12, 2017 
1.0 
Objectives 
1.1 Describe the purpose, specific aims, or objectives. 
We propose to study the effect of Acthar® on recovery from cognitive 
relapses in multiple sclerosis (MS).  Cognitive relapses are acute clinical 
declines in concentration, memory, working memory or increased 
fatigue.Cognitive relapses may also be detected by the presence on brain 
MRI of new active supratentorial Gad enhancing lesions. We will use 
well-validated, objective metrics to evaluate cognitive changes following 
treatment with a 5-day course of Acthar®over three months in patients 
showing cognitive relapses in MS. To account for the possible practice 
effects of cognitive testing over a three-month period, we will compare the 
results to a matched sample of MS patients who are clinically stable.     
1.2 State the hypotheses to be tested. 
The primary hypothesis of the study is that due to enhanced melanocortin 
response, Actharwill facilitate recovery from cognitive changes occurring 
during cognitively focused relapse, and that patients treated with Acthar 
will return to baseline following treatment.  
2.0 
Background 
2.1 Describe the relevant prior experience and gaps in current 
knowledge. 
Multiple sclerosis (MS) is an auto-immune disease causing inflammatory and 
neurodegenerative processes within the central nervous system (CNS).  
Supratentorial CNS damage has been shown to relate to cognitive impairment.1, 2 
The most common courses of MS (relapsing-remitting [RR] & secondary-
progressive [SP]) typically present as a series of acute exacerbations or ‘relapses’ 
wherein significant demyelination contributes to lesion activity and clinical 
changes, including cognitive deterioration.3  While the rate of relapse is likely to 
decline over time in patients with secondary-progressive MS, 
relapses/exacerbations are not uncommon in this population.   
 
Cognitiveimpairment constitutes a relevant clinical aspect of multiple sclerosis 
(MS). Depending on the disease phase and type, 40-65% of MS patients develop 
various degrees of cognitive dysfunction. These changes may begin very early in 
the disease process.4, 5 Difficulties with learning and memory and slowed 
information processing speed, along with difficulties in higher order functions 
such as abstraction, problem solving, and behavioral inhibition impact continued 
employment, daily function, and overall quality of life.6-10 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 6 of 46 
Revised: July 12, 2017 
Quantitative measurement of cognitive impairment in MS is frequently through 
neuropsychological evaluation (NP).  These evaluations are conducted by highly 
trained specialists, using a variety of psychometrically robust measures.12, 13 
These neuroperformancemeasures are validated through extensive study of their 
relationships to clinically relevant phenomena such as employment status, 
functional independence, and progression as detected by MRI.  Some examples of 
highly valid measures in MS are the Symbol Digit Modalities Test (SDMT),14 
Brief Visualspatial Memory Test- Revised (BVMT-R),15 and Paced Auditory 
Serial Addition Test (PASAT).16  Relevance of these measures has been 
demonstrated by their relationship to cortical atrophy,2, 17 employment,13 and 
more common methods of clinical assessment such as walking speed and manual 
dexterity.18 
 
While cognitive impairment over the span of the illness continues to be a focus of 
extensive research, few attempts have been made to study acute relapses with 
primarily cognitive sequelae (i.e., cognitive relapses).3, 11 This is due to the 
considerable methodological difficulties involved in studying the phenomenon.   
 
 
2.2 Describe any relevant preliminary data.  
A current study from our group, nearing completion, has demonstrated a 
substantial change in neuropsychological (NP) measures in MS patients with 
cognitive relapses (Benedict, et al. In Press) following treatment with high dose 
IV corticosteroids.  Corticosteroids have been shown to promote stabilization or 
improvement in randomized clinical trials following acute exacerbations19 by 
reducing inflammation and possibly promoting re-myelination, though evidence 
for this is still being sought.20, 21Though infusion administered corticosteroids are 
now accepted as the standard of care in the treatment of MS exacerbations, they 
are not without side effects and many patients find the infusion route of 
administration intolerable.  Alternate treatments, particularly those demonstrated 
to enhance recovery in functional domains, are vitally important.  
 
ACTH has been used for decades to treat MS exacerbations.  Recent data provides 
evidence that the beneficial effect of ACTH in other diseases (i.e. nephrotic 
syndrome, opsoclonus-myoclonus and infantile spasms) may be related not only 
to its direct induction of corticosteroid production, but also to a corticosteroid-
independent melanocortin path.22Melanocortins have anti-inflammatory and 
possible neuroprotective effects and have been shown to improve attention, 
memory and learning.  ACTH binding to central and peripheral melanocortin 
receptors downregulatesimmunocyte activity, an effect superimposed onto its 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 7 of 46 
Revised: July 12, 2017 
better known glucocorticoid-mediated actions.  In addition, ACTH potentiates 
parasympathetic and SNS activity. Both lessen immune responsiveness,22 and 
possibly provide neuroprotective effects.   
 
In addition to its effectiveness in treating cognitive relapses and the 
neuroprotective factors tentatively associated with its administration, ACTH may 
not only enhance initial recovery, but it may also slow the long-term progression 
of cognitive impairment.  Therefore, we propose to study the influence of Acthar 
on recovery from cognitive relapses in MS, and compare this to the influence of 
corticosteroid administration, as well as to stable MS patients.   
2.3 Provide the scientific or scholarly background for, rationale for, and 
significanceof the research based on the existing literatureand how 
will it add to existing knowledge. 
Response: The relative frequency of cognitive relapses is unknown at this time, 
though the current study and past studies along the same lines are the first to work 
towards this identification.  The measures mentioned above will be those used in 
identification of cognitive relapses when this topic is explored.  There is limited 
evidence that certain neuropsychological deficits detected during an acute relapse 
may be reversible, particularly in patients who initially have mild cognitive 
impairment, with improvement being in part correlated with the reduction in acute 
lesion load.3 
 
Both corticosteroids and adenocorticotropic hormone (Acthar) have been shown 
to promote stabilization or improvement in randomized clinical trials following 
acute exacerbations19 by reducing inflammation and possibly promoting 
remyelination, though evidence for this is still being sought.20, 21  IV 
Corticosteroids are typically the first choice for treatment, except in the case of 
patients intolerant to steroids or the infusion procedure, mostly driven by their 
lower cost.   
 
 
ACTH has been used for decades to treat MS exacerbations.  Recent data provides 
evidence that the beneficial effect of ACTH in other diseases (i.e. nephrotic 
syndrome, opsoclonus-myoclonus and infantile spasms ) may be related not only 
to its direct induction of corticosteroid production, but also to a corticosteroid-
independent melanocortin path.22Melanocortins have anti-inflammatory and 
possible neuroprotective effects and have been shown to improve attention, 
memory and learning.  ACTH binding to central and peripheral melanocortin 
receptors downregulatesimmunocyte activity, an effect superimposed onto its 
better known glucocorticoid-mediated actions.  In addition, ACTH potentiates 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 8 of 46 
Revised: July 12, 2017 
parasympathetic and SNS activity. Both lessen immune responsiveness,22 and 
possibly provide neuroprotective effects.   
 
In addition to its effectiveness in treating cognitive relapses and the 
neuroprotective factors tentatively associated with its administration, 
ACTH may not only enhance initial recovery, but it may also slow the 
long-term progression of cognitive impairment.  Therefore, we propose to 
study the influence of Acthar on recovery from cognitive relapses in 
MS,and to compare this to the influence of corticosteroid administration, 
as well as to stable MS patients. 
 
2.4 Include complete specific citations/references.  
1. 
Benedict RH, Zivadinov R. Predicting neuropsychological 
abnormalities in multiple sclerosis. J NeurolSci2006;245:67-72. 
2. 
Benedict R, Ramasamy D, Munschauer FE, Weinstock-Guttman 
B, Zivadinov R. Memory impairment in multiple sclerosis: correlation 
with deep gray matter and mesial temporal atrophy. Multiple Sclerosis 
2008;14:S252-S252. 
3. 
Foong J, Rozewicz L, Quaghebeur G, Thompson AJ, Miller DH, 
Ron MA. Neuropsychological deficits in multiple sclerosis after acute 
relapse. Journal of Neurology, Neurosurgery & Psychiatry 1998;64:529-
532. 
4. 
Feuillet L, Reuter F, Audoin B, et al. Early cognitive impairment 
in patients with clinically isolated syndrome suggestive of multiple 
sclerosis. MultScler2007;13:124-127. 
5. 
Glanz BI, Holland CM, Gauthier SA, et al. Cognitive dysfunction 
in patients with clinically isolated syndromes or newly diagnosed multiple 
sclerosis. MultScler2007;13:1004-1010. 
6. 
Simmons RD, Tribe KL, McDonald EA. Living with multiple 
sclerosis: longitudinal changes in employment and the importance of 
symptom management. Journal of Neurology 2010;257:926-936. 
7. 
Benedict RHB, Zivadinov R. Risk factors for and management of 
cognitive dysfunction in multiple sclerosis. Nat Rev Neurol2011;7:332-
342. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 9 of 46 
Revised: July 12, 2017 
8. 
Patti F, Pozzilli C, Montanari E, et al. Effects of education level 
and employment status on HRQoL in early relapsing-remitting multiple 
sclerosis. MultScler2007;13:783-791. 
9. 
Amato MP, Ponziani G, Rossi F, Liedl CL, Stefanile C, Rossi L. 
Quality of life in multiple sclerosis: the impact of depression, fatigue and 
disability. Multiple Sclerosis 2001;7:340-344. 
10. 
Amato MP, Ponziani G, Siracusa G, Sorbi S. Cognitive 
dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. 
Archives of Neurology 2001;58:1602-1606. 
11. 
Morrow SA, Jurgensen S, Forrestal F, Munchauer FE, Benedict 
RHB. Effects of acute relapses on neuropsychological status in multiple 
sclerosis patients. Journal of Neurology 2011;258:1603-1608. 
12. 
Benedict RH, Fischer JS, Archibald CJ, Arnett PA, Beatty WW, 
Bobholz J, et al. Minimal Neuropsychological Assessment of MS Patients: 
A Consensus Approach. Clinical Neuropsychologist 2002;16:381-397. 
13. 
Benedict RH, Cookfair D, Gavett R, et al. Validity of the minimal 
assessment of cognitive function in multiple sclerosis (MACFIMS). J 
IntNeuropsycholSoc2006;12:549-558. 
14. 
Smith A. Symbol digit modalities test: Manual. Los Angeles: 
Western Psychological Services, 1982. 
15. 
Benedict R. Brief Visuospatial Memory Test - Revised: 
Professional Manual. Odessa, Florida: Psychological Assessment 
Resources, 1997. 
16. 
Gronwall D. Paced auditory serial addition task: A measure of 
recovery from concussion. Perceptual and Motor Skills 1977;44:367-373. 
17. 
Benedict RHB, Bruce J, Dwyer MG, et al. Diffusion-weighted 
imaging predicts cognitive impairment in multiple sclerosis. Multiple 
Sclerosis 2007;13:722-730. 
18. 
Benedict RHB, Holtzer R, Motl RW, et al. Upper and Lower 
Extremity Motor Function and Cognitive Impairment in Multiple 
Sclerosis. J IntNeuropsycholSoc2011;17:643-653. 
19. 
Filippini G, Brusaferri F, Sibley W, et al. Corticosteroids or ACTH 
for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev 
2000;CD001331. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 10 of 46 
Revised: July 12, 2017 
20. 
Shah A, Eggenberger E, Zivadinov R, Stuve O, Frohman EM. 
Corticosteroids for multiple sclerosis: II. Application for disease-
modifying effects. Neurotheraputics2007;4:627-632. 
21. 
Frohman EM, Shah A, Eggenberger E, Metz L, Zivadinov R, 
Stuve O. Corticosteroids for multiple sclerosis: I. Application for treating 
MS exacerbations. . Neurotheraputics2007;4:618-626. 
22. 
Arnason B, Berkovich R, Catania A, Lisak R, Zaidi M. 
Mechanisms of action of adrenocorticotropic hormone and other 
melanocortins relevant to the clinical management of patients with 
multiple sclerosis. Multiple Sclerosis Journal 2012. 
23. 
Fischer JS, Rudick RA, Cutter GR, Reingold SC. The Multiple 
Sclerosis Functional Composite Measure (MSFC): an integrated approach 
to MS clinical outcome assessment. National MS Society Clinical 
Outcomes Assessment Task Force. Multiple Sclerosis 1999;5:244-250. 
24. 
Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction 
in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 
1991;41:685-691. 
25. 
Gronwall DMA. Paced auditory serial addition task: A measure of 
recovery from concussion. Perceptual and Motor Skills 1977;44:367-373. 
26. 
Benedict RHB, Schretlen D, Groninger L, Dobraski M, Shpritz B. 
Revision of the Brief Visuospatial Memory Test: Studies of normal 
performance, reliability, and validity. Psychological Assessment 
1996;8:145-153. 
27. 
Benedict RHB. Brief Visuospatial Memory Test - Revised: 
Professional Manual. Odessa, Florida: Psychological Assessment 
Resources, Inc, 1997. 
28. 
Benedict RHB, Munschauer F, Linn R, et al. Screening for 
multiple sclerosis cognitive impairment using a self-administered 15-item 
questionnaire. Multiple Sclerosis 2003;9:95-101. 
29. 
Kurtzke JF. Rating neurologic impairment in Multiple-Sclerosis - 
An Expanded Disability Status Scale (EDSS). Neurology 1983;33:1444-
1452. 
30. 
Gilson BS, Gilson JS, Bergner M, et al. Sickness impact profile - 
Development of an outcome measure of health-care. Am J Public Health 
1975;65:1304-1310. 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 11 of 46 
Revised: July 12, 2017 
3.0 
Inclusion and Exclusion Criteria 
3.1 Describe the criteria that define who will be included or excluded in 
your final study sample. 
Inclusion Criteria: 
(1) Identification by clinical care provider of new acute (defined by 
clinician as a symptom of recent origin developing with a time span of 48 
hours) cognitive relapse or supratentorial GAD enhancing lesions on MRI 
with confirmation of cognitive decline.    
 
(1a) Confirmation of cognitive decline will be obtained by 
administering the SDMT as a screening procedure for the study.  
Participants will qualify if they show a > -3 raw score point change 
onSDMT (relative to baseline identified to meet criteria #4).  
(2) Males/Females between the ages of 18-65 years who are capable of 
understanding and complying with the protocol, speak and write fluent 
English, and have at least a 9th grade education. 
(3) Have a diagnosis of Relapsing Remitting or early Secondary 
Progressive MS as per revised McDonald’s Criteria.  
(4) Valid NP testing in the past 4-5 years 
(5) EDSS of ≤ 7.0 
(6) Have given written informed consent prior to any study-related 
procedure not part of normal medical care, with the understanding that 
consent may be withdrawn by the subject at any time without prejudice to 
his/her future medical care. 
(7) Are capable of performing the requirements of a NP test battery 
including at least 20/70 near visual acuity by near vision chart, with 
correction. 
 
Exclusion Criteria:  
(1) Have cognitive deficits caused by concomitant medication usage or 
other significant neurological/psychological disease e.g. Alzheimer’s 
disease, Parkinson’s disease, stroke, transient ischemic attack, Vascular 
Dementia, Huntington’s disease, traumatic brain injury, or chronic CNS 
infection. 
(2) Have evidence of any other medical cause(s) of cognitive impairment.  


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 12 of 46 
Revised: July 12, 2017 
(3) Have evidence of current major depression as determined by a positive 
BDI-FS and clinician interview. 
(4) Clear new physical signs or symptoms that are referable to the spinal 
cord, brainstem, or optic nerve. 
(5) Evidence on MRI of new lesions in the brainstem, spinal cord, or optic 
nerve. 
(6) Patients with changes to medications known to influence cognition 
(narcotics, stimulants, etc.) or to disease modifying therapy within one 
month of study initiation (or within a timeframe deemed high risk by 
treating physician) will be excluded. 
(7) Presence of current infections as determined by clinician interview. 
(8) Currently nursing, intentionally seeking pregnancy, or deemed at-risk 
for unplanned pregnancy. 
(9) Any concomitant medication, or medical condition contraindicated 
with Acthar. 
 
3.2 Describe how individuals will be screened for eligibility. 
All participants will undergo study eligibility screening and consenting by 
a Clinical Research Project Coordinator.  The participants will be provided 
with a description of the required testing for study participation, and any 
risks will be described in order for the person to make an informed 
decision regarding voluntary study participation. This is also an 
opportunity for the person to ask questions regarding the study and the 
testing components.  All study participants who choose to enroll in the 
study will be asked to sign and date the consent form in front of the Study 
Coordinator. 
 
3.3 Indicate specifically whether you will include or exclude each of the 
following special populations:(You may not include members of 
these populations as subjects in your research unless you indicate 
this in your inclusion criteria.) 
 
Adults unable to consent 
 
Individuals who are not yet adults (infants, children, teenagers) 
 
Pregnant women 
 
Prisoners 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 13 of 46 
Revised: July 12, 2017 
 
Inclusion criteria state subjects must be willing and able to comply with 
study procedures for the duration of the study.  
 
Individuals under the age of 18 will not be included 
 
Pregnant women will not be included 
 
Prisoners will not be included 
3.4 Indicate whether you will include non-English speaking individuals.  
Provide justification if you will exclude non-English speaking 
individuals.  
(In order to meet one of the primary ethical principles of equitable 
selection of subjects, non-English speaking individuals may not be 
routinely excluded from research.  In cases where the research is of 
therapeutic intent or is designed to investigate areas that would 
necessarily require certain populations who may not speak English, 
the researcher is required to make efforts to recruit and include non-
English speaking individuals.  However, there are studies in which it 
would be reasonable to limit subjects to those who speak English: 
e.g., pilot studies, small unfunded studies with validated instruments 
not available in other languages, numerous questionnaires, and 
some non-therapeutic studies which offer no direct benefit.)  
 
We will not be including non-English speaking individuals.  All 
neuropsychological measures are given in English and have not yet been 
translated or validated in other languages. 
 
4.0 
Study-Wide Number of Subjects (Multisite/Multicenter Only) 
4.1 If this is a multicenter study, indicate the total number of subjects to 
be accrued across all sites. 
N/A 
 
5.0 
Study-Wide Recruitment Methods (Multisite/Multicenter Only) 
If this is a multicenter study and subjects will be recruited by methods not under 
the control of the local site (e.g., call centers, national advertisements) describe 
those methods.  Local recruitment methods are described later in the protocol. 
5.1 Describe when, where, and how potential subjects will be recruited. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 14 of 46 
Revised: July 12, 2017 
N/A 
 
5.2 Describe the methods that will be used to identify potential subjects. 
N/A 
 
5.3 Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For advertisements, 
attach the final copy of printed advertisements. When advertisements 
are taped for broadcast, attach the final audio/video tape. You may 
submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB 
reviews the final audio/video tape.) 
N/A 
 
6.0 
Multi-Site Research (Multisite/Multicenter Only) 
6.1 If this is a multi-site study where you are the lead investigator, 
describe the processes to ensure communication among sites, such 
as: 
 
All sites have the most current version of the protocol, consent 
document, and HIPAA authorization. 
 
All required approvals have been obtained at each site 
(including approval by the site’s IRB of record). 
 
All modifications have been communicated to sites, and 
approved (including approval by the site’s IRB of record) 
before the modification is implemented. 
 
All engaged participating sites will safeguard data as required 
by local information security policies. 
 
All local site investigators conduct the study appropriately. 
 
All non-compliance with the study protocol or applicable 
requirements will reported in accordance with local policy. 
N/A 
 
6.2 Describe the method for communicating to engaged participating 
sites: 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 15 of 46 
Revised: July 12, 2017 
 
Problems. 
 
Interim results. 
 
The closure of a study 
N/A 
 
7.0 
Study Timelines 
7.1 Describe the duration of an individual subject’s participation in the 
study. 
This is a prospective, open-label study of Acthar administered as treatment 
for an acute cognitive relapse.  Primary and secondary endpoints will be 
collected prior to Acthar administration and at 3-month follow-up.  
Comparison will be made to a stable MS control group.   
7.2 Describe the duration anticipated to enroll all study subjects. 
Enrollment of all study participants is expected to take 4 years (48 
months). 
 
7.3 Describe the estimated date for the investigators to complete this 
study (complete primary analyses) 
Completion of this study, including primary analysis, is expected within 5 
years. 
8.0 
Study Endpoints 
8.1 Describe the primary and secondary study endpoints. 
Primary measures will include: Symbol Digit Modalities Test,14 Brief 
Visualspatial Memory Test- Revised,15 Paced Auditory Serial Addition Test,16and 
the Multiple Sclerosis Functional Composite (MSFC).23These tests are some of 
the strongest indicators of clinically relevant cognitive change available in MS. 
 
The Symbol Digit Modalities Test (SDMT) will be used to measure visual 
processing speed.  This test presents a stimulus key of numbers paired with 
abstract symbols at the top of a page.  Participants scan the page below the key 
which has rows of symbols without the paired numbers.  The task is to generate 
the associated numbers orally as fast as possible.  We will employ the Rao oral 
adaptation 24 of the SDMT as the oral presentation has been deemed most 
appropriate for use with a potentially motor impaired population.12 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 16 of 46 
Revised: July 12, 2017 
The Paced Auditory Serial Addition Test (PASAT)25 3 sec interval version will be 
used as an indicator of working memory performance.  The PASAT is an auditory 
task in which subjects are exposed to single digit numbers voiced every three 
seconds.  After each number presentation, the subject’s task is to respond with the 
sum of the last two digits presented.  As each new number is presented, the 
subject must recall the previous digit, add them together, and respond before the 
next number is presented.   
 
The Multiple Sclerosis Functional Composite (MSFC)23 is a composite measure 
incorporating aspects of cognition, walking speed and manual dexterity.  The 25-
foot walk, 9-hole peg test, and PASAT 3-sec (described above) are normalized 
based on an established normative sample and an overall composite z- score is 
then determined.  This composite is frequently used as a primary outcome in 
clinical trials as it covers three major domains of function potentially impaired in 
MS. 
 
The Brief Visuospatial Memory Test  Revised (BVMTR)26, 27 is a measure of 
episodic memory.  This task presents a display of six visual designs presented on 
an 8.5 x 11 piece of paper for three consecutive learning trials.  During each trial 
the stimulus is presented for 10 seconds, after which the participant is asked to 
draw the figures as accurately as possible in their correct locations.  The six 
designs receive a score of 0, 1, or 2 based on accuracy and location.  After a 20-25 
minute delay, participants are again asked to recall and draw the designs.   
 
The North American Adult Reading Test (NAART) is a measure of verbal ability. 
Patients are asked to read a list of words aloud.  
 
Secondary measures will include: self and informant ratings of cognitive 
problems using the Multiple Sclerosis Neuropsychological Questionnaire,28 the 
Expanded Disability Status Scale,29 the Multiple Sclerosis Impact Scale, the Beck 
Depression Inventory – Fast Screen, and subscales from the Sickness Impact 
Profile30 (an assessment of health related quality of life and activities of daily 
living).  Incidence of adverse events and concurrent medications will also be 
recorded as potential covariates. 
 
8.2 Describe any primary or secondary safety endpoints. 
N/A  
 
9.0 
Procedures Involved 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 17 of 46 
Revised: July 12, 2017 
9.1 Describe and explain the study design. 
 
9.2 Provide a description of all research procedures being performed 
and when they are performed, including procedures being performed 
to monitor subjects for safety or minimize risks. 
Initial referral will be initiated by treating physicians. Following 
confirmation of the subject’s relapse status and/or the presence of new 
supratentorial GAD enhancing lesions, patients deemed eligible for Acthar 
treatment will be screened for symptoms of infection and evaluated by 
their treating physician.  If the patient agrees, the clinician will contact the 
research coordinator with the referral. 
At this time, all participants will undergo study eligibility screening and 
consent by a Clinical Research Project Coordinator. The project 
coordinator or a designated member of the research team will meet, in 
person, with the participant to discuss the study objectives and procedures, 
so that he/she can make an informed decision regarding voluntary study 
participation. Participants will have an opportunity to ask questions 
regarding the study, procedures, etc. At this time, the study coordinator 
will administer the SDMT to the relapsing patient.  The study coordinator 
will give this score to another study personnel.  At this time the other 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 18 of 46 
Revised: July 12, 2017 
study personnel will check the patient’s baseline SDMT score.  If this 
score is less than or equal to a 3 point decline, the patient will be deemed 
eligible for the study.  Participants who choose to enroll in the study will 
then be asked to sign and date a consent form in front of the Study 
Coordinator. 
As described above, enrolled subjects will complete the full cognitive 
baseline assessment [CVLT2 Learning → BVMTR Learning → SDMT → 
PASAT → DKEFS Sorting → CVLT2 Delayed Recall → BVMTR 
Delayed Recall → NAART].  Here the SDMT will be administered a 
second time to complete the run in for the information processing speed 
[IPS] composite. Participants will then be guided to complete other patient 
report questionnaires [BDIFS, FSS MSIS, MSNQ]. Finally, measures of 
motor function and clinical status will be assessed (EDSS and MSFC). 
Acthar Gel will then be administered by a research coordinator to the 
relapsing patient in accordance with the recommendations set forth in the 
package insert.  The dosage may be individualized according to the 
medical condition of each patient.  Frequency and dose of the drug may be 
determined by considering the severity of the disease and the initial 
response of the patient. Acthar will be provided through the study. 
As cognitive relapses are typically milder (compared tophysically focused 
relapses) subjects will be initially dosed for 5 days and pending clinical 
response or adverse events treatment may be continued for the full 2 
weeks in the opinion of the investigator.  At study enrollment participants 
will be instructed on self-administration procedure and supplied with a 5-
day course of Acthar® Gel (5ml/80 IU).  Medication will be administered 
through either subcutaneous or intramuscular self-injection (selected by 
the patient).  Patients will be instructed by trained clinical staff on self-
administration and will self-administer the first injection under 
observation in the clinic. 
The neuropsychological evaluation takes approximately 45 minutes to 
complete.  The neurological exam takes about 15 minutes.  Training and 
administration of the drug takes about 15 minutes.  The 
neuropsychological assessment will be repeated at 90 days. All 
participants will be given $200 at the completion of the study.  At the time 
of consenting, each participant will complete a W-9 form.  Checks will be 
mailed from our billing department directly to the participant’s address of 
choice.   
The treating neurologist will be responsible for identifying patients 
agreeing to treatment with the study drug and for insuring that the EDSS is 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 19 of 46 
Revised: July 12, 2017 
conducted in a valid manner.  Examining technicians will be responsible 
for administering the neuropsychological testing battery.  The Research 
Coordinator will be responsible for consenting patients, and contacting 
them on day 7 and day 30 to evaluate for concomitant medications and 
adverse events. The PI will be responsible for consenting patients, 
coordinating the database, conducting statistical analysis, coordinating 
recruitment efforts, and presenting the data. 
A detailed clinical assessment will precede enrollment and only patients 
who agree to be treated with Acthar will be approached for 
participation.For patients that qualify, Acthar will be provided through the 
study.  
All medications prescribed for patients will be monitored as per PI 
recommendations. Patients will be evaluated and monitored and all SAEs 
will be reported to the local IRB within required timelines. 
 
9.3 Describe procedures performed to lessen the probability or 
magnitude of risks. 
A detailed clinical assessment will precede enrollment and only patients 
who agree to be treated with Acthar will be considered for participation.   
All serious adverse events will be reported to Mallinckrodt (formerly 
Questcor) and local IRB within required timelines.  The study protocol 
will be approved by the local Health Sciences Institutional Review Board 
at the University at Buffalo.  
The Research Coordinator will be responsible for consenting patients, and 
contacting them on day 7 and day 30 to evaluate for concomitant 
medications and adverse events.  Subjects will also be given the telephone 
contact information for study staff in case of any late-emerging side 
effects.  Any adverse events will be reported to the PI, the patient’s 
treating neurologist, and the Health Sciences Institutional Review Board at 
the University at Buffalo Immediately. 
Prior to any testing under this protocol, including screening tests and 
evaluations, all subjects will sign an informed consent form that complies 
with the requirements of both 21 CFR Part 50 and HIPAA before entering 
the study.  Or, a consent form that complies with the requirements of 21 
CFR Part 50 and a separate HIPAA compliant authorization form for the 
use of and disclosure of the subject’s protected health information (PHI) 
will be obtained from the subject in accordance with local practice and 
regulations. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 20 of 46 
Revised: July 12, 2017 
The background of the proposed study and the benefits and risks of the 
procedures and study will be explained to the subject.  A copy of the 
informed consent document signed and dated by the subject will be given 
to the subject.  Confirmation of a subject’s informed consent will also be 
documented in the subject’s medical records prior to any testing under this 
protocol, including screening tests and evaluations. 
The subject will not be identified by name in any study reports, and these 
reports will be used for research purposes only.  Every effort will be made 
to keep the subject’s personal medical data confidential. 
All medications prescribed for patients will be monitored as per PI 
recommendations. Patients will be evaluated and monitored and all SAEs 
will be reported to the local IRB within required timelines. 
SAEs and unexpected AEs will be collected by the investigator.  An SAE 
is defined as an adverse event that meets any of the following criteria: 
results in death, is life-threatening, requires hospitalization or prolongation 
of existing hospitalization, results in disability/incapacity, is a congenital 
anomaly/birth defect, or is an important medical event.  An unexpected 
adverse event is an AE either not previously reported or for which the 
nature, seriousness, severity, or outcome is not consistent with the current 
Investigator’s Brochure.  Additionally, the site should report if a patient 
becomes pregnant during the study and track until an outcome is known.  
AEs will be documented, evaluated and treated by the investigators 
according to standard of care (decisions regarding treatment will be made 
by Investigator Bianca Weinstock-Guttman, MD).  All SAEs will be 
reported to the Institutional Review Board (IRB), as well as RTI-HS (on 
behalf of Mallinckrodt, formerly Questcor), within 5 business days (unless 
a different notification schedule is required by the IRB).  In the event of a 
patient death, initial notice will be provided to the IRB and RTI-HS within 
24 hours and full details regarding the case will be provided within 5-
calendar days.  Safety reporting guidelines and relevant forms are supplied 
in Appendix 1. 
 
9.4 Describe all drugs and devices used in the research and the purpose 
of their use, and their regulatory approval status. 
Acthar Gel will be administered in accordance with the recommendations 
set forth in the package insert.  The dosage may be individualized 
according to the medical condition of each patient.  Frequency and dose of 
the drug may be determined by considering the severity of the disease and 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 21 of 46 
Revised: July 12, 2017 
the initial response of the patient. Acthar Gel will be provided to the 
patient through the study. 
As cognitive relapses are typically milder (compared tophysically focused 
relapses) subjects will be initially dosed for 5 days and pending clinical 
response or adverse events treatment may be continued for the full 2 
weeks in the opinion of the investigator.  At study enrollment participants 
will be instructed on self-administration procedure and supplied with a 5-
day course of Acthar® Gel (5ml/80 IU).  Medication will be administered 
through either subcutaneous or intramuscular self-injection (selected by 
the patient).  Patients will be instructed by trained clinical staff on self-
administration and will self-administer the first injection under 
observation in the clinic. 
 
9.5 Describe the source records that will be used to collect data about 
subjects. (Attach all surveys, scripts, and data collection forms.) 
Source records include: 
• 
Expanded Disability Status Scale (EDSS) 
• 
Symbol Digit Modalities Test (SDMT) 
• 
Paced Auditory Serial Addition Test (PASAT) 
• 
California Verbal Learning Test Second Edition (CVLT2) 
• 
Brief Visuospatial Memory Test- Revised (BVMT-R) 
• 
MS Functional Composite (MSFC) 
• 
Beck Depression Inventory Fast Screen (BDIFS) 
• 
Fatigue Severity Scale (FSS) 
• 
Multiple Sclerosis Impact Scale (MSIS) 
• 
MS Neuropsychological Screening Questionnaire (MSNQ) 
• 
North American Adult Reading Test (NAART) 
9.6 What data will be collected including long-term follow-up. 
The above-mentioned data will be collected at months 0 and 3. 
9.7 For HUD uses provide a description of the device, a summary of 
how you propose to use the device, including a description of any 
screening procedures, the HUD procedure, and any patient follow-
up visits, tests or procedures. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 22 of 46 
Revised: July 12, 2017 
N/A 
 
10.0 Data and Specimen Banking 
10.1 If data or specimens will be banked for future use, describe where 
the data/specimens will be stored, how long they will be stored, how 
the data/specimens will be accessed, and who will have access to the 
data/specimens. 
Neuropsychological testing data and clinical outcome measures will be 
maintained in de-identified participant charts. These charts will be stored 
in a locked cabinet and entered into a password-protected database. 
Appropriate legal guidelines regarding retention of records will be 
followed. Identifiable data will be destroyed at the earliest possible point. 
The subject will not be identified by name in any study reports, and these 
reports will be used for research purposes only.  Every effort will be made 
to keep the subject’s personal medical data confidential. Stored data will 
be accessed only by the PI and/or designated research staff. The use of 
stored, de-identified data is undetermined at this time. 
 
10.2 List the data to be stored or associated with each specimen. 
Neuropsychological testing data and clinical outcome measures will be 
stored for each participant. 
10.3 Describe the procedures to release data or specimens, including: the 
process to request a release, approvals required for release, who 
can obtain data or specimens, and the data to be provided with 
specimens. 
Identifiable data will not be released to any outside sources. Investigator 
will refer to the Clinical Trial Agreement for details regarding the 
disclosure of study results. 
11.0 Data Management 
11.1 Describe the data analysis plan, including any statistical 
procedures. 
Data will be processed by trained research assistants blind to study 
hypotheses.  Analysis will be conducted using SPSS 22.0.  Analysis 
strategy will be repeated measures analysis of variance where baseline, 
day 0 and day 90 scores are compared.  Analysis of variance will be used 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 23 of 46 
Revised: July 12, 2017 
to compare the magnitude of change between day 0 and 90 between the 
MS patients treated with Acthar and the previously collected controls.  
Analysis of variance will also be used to compare the magnitude of 
cognitive recovery after corticosteroid treatment to that after Acthar 
treatment. 
The difference between the means at Day 0 and Day 90 will be used to 
calculate Cohen’s d for each group.  To facilitate analysis, all data will be 
normalized using a large previously published control sample.13All tests 
will be performed based on an alpha of 0.05.  Net effect sizes removing 
estimated practice effects will be calculated using Cohen’s d.  
11.2 Provide a power analysis. 
The selection of 30 as the target enrollment is based on the previously 
completed study of 25 relapsing and 25 stable MS patients.  Five 
additional patients are planned in order to increase the power of 
subsequent analyses.   A power analysis based on the observed effect of 
corticosteroids in the relapsing group of d = .56 with 30 participants will 
be powered >85% to detect effects of a moderate magnitude from Acthar. 
11.3 Describe the steps that will be taken secure the data (e.g., training, 
authorization of access, password protection, encryption, physical 
controls, certificates of confidentiality, and separation of identifiers 
and data) during storage, use, and transmission. 
All clinical and neurometric assessments will be conducted under the 
supervision of the PI. All members of research team will complete 
relevant training programs and courses, including but not limited to: 
HIPAA, CITI and GRP.  
NP testing data will be maintained in locked filing cabinets within a 
locked room (4085) within UBMD Neurology at the Conventus Center, 
1001 Main Street, Buffalo, NY 14203. Participants will be assigned study 
identification numbers at enrollment. The NP testing database will be kept 
without identifying information on an encrypted computer and matched to 
online survey information using the assigned code number. 
The subject will not be identified by name in any study reports, and these 
reports will be used for research purposes only.  Every effort will be made 
to keep the subject’s personal medical data confidential. 
 
11.4 Describe any procedures that will be used for quality control of 
collected data. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 24 of 46 
Revised: July 12, 2017 
A Data and Safety Monitor (DSM), comprised of an independent member 
of the MS-care community without a conflict of interest with the study, 
will be selected for this study. It will be comprised of a medical 
professional who is not involved with the conduct of the trial. The DSM 
will be responsible for evaluating scientific issues related to the study.  
The DSM will meet with the investigators upon the enrollment of every 10 
participants and/or in the event that any adverse, serious or non-serious 
event occurs, and/or every 6 months or more frequently if deemed 
necessary. The DSM will be given a detailed progress report before the 
scheduled meeting. This report will contain safety data summaries: 
recruitment, visit schedules, missed visits, patient compliance, 
demographics, outcomes, and adverse events.  In addition, copies of all 
Adverse Events will be included in the report. Also, the DSM will be able 
to request specific information and analyses to be used for monitoring 
purposes at any time during the study. 
The roles and responsibilities of the DSM will include the following: 
• 
Review protocol, informed consent documents, plans for data 
safety and monitoring; 
• 
Evaluate study progress, including periodic assessments of data 
quality and other factors that may affect study outcome; 
• 
Consider external factors such as scientific or therapeutic 
developments that may impact the safety of the participants or the 
ethics of the trial; 
• 
Protect the safety and scientific progress of the trial; 
• 
Make recommendations to the Investigators regardingcontinuation, 
termination, or other modifications to the study based on observed 
beneficial or adverse events of the treatment under study. 
 
11.5 Describe how data and specimens will be handled study-wide: 
Neuropsychological testing data will be kept in a locked room and in a 
locked cabinet. After data scoring and entry, neuropsychological testing 
files will be de-identified by blacking out identification information. 
Databases will be password protected. 
 
11.6 What information will be included in that data or associated with the 
specimens? 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 25 of 46 
Revised: July 12, 2017 
Each participant will be assigned a study identification number. Data 
points related to information processing speed, memory, executive 
functioning, depression, fatigue, and disability will be collected. 
11.7 Where and how data or specimens will be stored? 
Neuropsychological testing data will be kept in a locked room and in a 
locked cabinet. 
11.8 How long the data or specimens will be stored? 
De-identified data will be stored for the remainder of the study and 
according to appropriate legal guidelines regarding retention of records. 
De-identified data may be stored indefinitely for future studies, not yet 
determined.  
11.9 Who will have access to the data or specimens? 
Trained staff under Dr. Ralph Benedict (Primary Investigator) directly 
involved in the conduct of this study will have access to data.Identifiable 
data will not be released to any outside sources. Investigator will refer to 
the Clinical Trial Agreement for details regarding the disclosure of study 
results. 
11.10Who is responsible for receipt or transmission of the data or 
specimens? 
Identifiable data will not be released to any outside sources. Investigator 
will refer to the Clinical Trial Agreement for details regarding the 
disclosure of study results. 
 
11.11How data and specimens will be transported? 
N/A 
 
12.0 Provisions to Monitor the Data andEnsure the Safety of Subjects 
12.1 Describe the plan to periodically evaluate the data collected 
regarding both harms and benefits to determine whether subjects 
remain safe. 
Patients will be assessed for general safety and asked about potential 
adverse events on day 7 and day 30. 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 26 of 46 
Revised: July 12, 2017 
12.2 Describe what data are reviewed, including safety data, untoward 
events, and efficacy data. 
Data being reviewed will be patient self-report of general safety and 
potential adverse events. 
 
12.3 Describe how the safety information will be collected (e.g., with case 
report forms, at study visits, by telephone calls with participants). 
Safety information will be collected at each study visit and via telephone 
on day 7 and day 30. 
 
12.4 Describe the frequency of data collection, including when safety 
data collection starts. 
Neuropsychological and clinical outcome data will be collected at day 0 
and day 90.  Information on safety of patient will be collected via 
telephone on day 7 and day 30. 
 
12.5 Describe who will review the data. 
Designated, trained staff under Dr. Ralph Benedict (Primary Investigator) 
will review neuropsychological, clinical outcome, and safety data.  A Data 
and Safety Monitor (DSM) will also review recruitment, visit schedules, 
missed visits, patient compliance, demographics, outcomes, and adverse 
events. 
12.6 Describe the frequency or periodicity of review of cumulative data. 
Neuropsychological, clinical outcome and safety data will be reviewed at 
each data collection and additionally by the Data and Safety Monitor 
(DSM) upon the enrollment of every 10 participants and/or in the event 
that any adverse, serious or non-serious event occurs, and/or every 6 
months or more frequently if deemed necessary. 
 
12.7 Describe the statistical tests for analyzing the safety data to 
determine whether harm is occurring. 
N/A 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 27 of 46 
Revised: July 12, 2017 
12.8 Describe any conditions that trigger an immediate suspension of the 
research. 
N/A 
 
13.0 Withdrawal of Subjects 
13.1 Describe anticipated circumstances under which subjects will be 
withdrawn from the research without their consent. 
Circumstances that could possibly lead to the withdrawal of a subject 
without his or her consent would be if continuation of treatment with 
Actharwas no longer in the patient’s best interest, based on treating 
clinician judgment. The treating clinician may remove subjects from the 
study at any time should he/she feel it is no longer in the subject’s best 
interest or if the patient is non-compliant with study procedures. 
 
13.2 Describe any procedures for orderly termination. 
In the event of early termination/withdrawal from the study, an in-person 
exit interview will be conducted by the PI, treating clinician or trained 
members of the research team. 
13.3 Describe procedures that will be followed when subjects withdraw 
from the research, including partial withdrawal from procedures 
with continued data collection. 
Participation in this study is voluntary.  Patients being treated with the 
study medication may refuse to participate without penalty and such 
refusal will not prejudice future treatment or benefits at the UBMD 
Neurology.  Patients will be free to discontinue participation in the study 
at any time without fear of penalty or loss of medical care or loss of any 
benefits to which you may otherwise be entitled. If a subject chooses to 
withdraw from the study, the data collected up to the time of withdrawal 
will continue to be used, but the subject will no longer be contacted and no 
further data will be collected. 
14.0 Risks to Subjects 
14.1 List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the subjects related the subjects’ participation in 
the research. Include as may be useful for the IRB’s consideration, a 
description of the probability, magnitude, duration, and reversibility 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 28 of 46 
Revised: July 12, 2017 
of the risks. Consider physical, psychological, social, legal, and 
economic risks. 
Risks 
There are no risks associated with the neurological examination. 
The risks associated with the tests and questionnaires are minimal; there is 
the possibility that subjects mayexperience some fatigue or frustration.  
The examiners will do their best to minimize them. 
The side effects that may occur with Acthar® are related primarily to its 
steroid-like effects similar to IV Solumedrol.  There may be increased 
susceptibility to new infection and increased risk of reactivation of latent 
infections, hence the strict eligibility criteria.  
Acthar® may cause various side effects such as: 
• 
Dizziness 
• 
Nausea 
• 
Anaphylactic or hypersensitivity reactions 
• 
Hypertension (high blood pressure) 
• 
Congestive heart failure 
• 
Thin, fragile skin 
• 
Erythema (redness of the skin) 
• 
Increased sweating 
• 
Increased requirements for insulin or oral hypoglycemic (low 
blood sugar) agents in diabetics 
• 
Elevated blood sugar 
• 
Cushing’s syndrome 
• 
Gastrointestinal perforation and bleeding or peptic ulcer 
• 
Pancreatitis (inflammation of the pancreas) 
• 
Abdominal distension (enlargement) 
• 
Water retention 
• 
Peripheral edema (swelling of the extremities) 
• 
Headache 
• 
Impaired wound healing 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 29 of 46 
Revised: July 12, 2017 
• 
Ecchymosis (bruising) 
• 
Menstrual irregularities 
• 
Loss of muscle mass 
• 
Thinning of the bones 
• 
Cataracts 
• 
Glaucoma 
• 
Onset or worsening of euphoria, insomnia, irritability, mood 
swings, personality changes, depression, anxiety and psychosis 
• 
Fatigue 
• 
Injection site pain 
Pregnancy 
Women of childbearing potential should not become pregnant during the 
period of the study. The effect of Acthar® on an unborn baby (fetus) is 
unknown. If a patient becomes pregnant, continuing the study drug may 
not be safe for their unborn baby and for themselves.  The patient will be 
advised to report the pregnancy immediately to the site’s staff and subject 
will be removed from the study. 
 
14.2 If applicable, indicate which procedures may have risks to the 
subjects that are currently unforeseeable. 
There may be other side effects of Actharwhich are unknown at this time. 
All patients will be monitoredcarefully for any side effects and will be 
instructed to report any concerns or changes in their condition to their 
neurologist. Patients will also be provided 24/7 access to a cellular 
telephone number used only for research purposes. 
14.3 If applicable, indicate which procedures may have risks to an 
embryo or fetus should the subject be or become pregnant. 
Women of childbearing potential should not become pregnant during the 
period of the study. The effect of Acthar® on an unborn baby (fetus) is 
unknown. If a patient becomes pregnant, continuing the study drug may 
not be safe for their unborn baby and for themselves.  The patient will be 
advised to report the pregnancy immediately to the site’s staff and subject 
will be removed from the study. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 30 of 46 
Revised: July 12, 2017 
14.4 If applicable, describe risks to others who are not subjects. 
N/A 
 
15.0 Potential Benefits to Subjects 
15.1 Describe the potential benefits that individual subjects may 
experience from taking part in the research. Include as may be 
useful for the IRB’s consideration, the probability, magnitude, and 
duration of the potential benefits. 
There is no direct benefit for participating in this study.  However, 
participation may help doctors to learn more about treatments that may 
help people with MS who have cognitive difficulties. 
15.2 Indicate if there is no direct benefit. Do not include benefits to 
society or others. 
There is no direct benefit to subjects participating in the study. 
16.0 Vulnerable Populations 
16.1 If the research involves individuals who are vulnerable to coercion 
or undue influence, describe additional safeguards included to 
protect their rights and welfare. 
 
If the research involves pregnant women, review 
“CHECKLIST: Pregnant Women (HRP-412)” to ensure that 
you have provided sufficient information. 
 
If the research involves neonates of uncertain viability or non-
viable neonates, review “CHECKLIST: Neonates (HRP-413)” 
or “HRP-414 – CHECKLIST: Neonates of Uncertain Viability 
(HRP-414)” to ensure that you have provided sufficient 
information. 
 
If the research involves prisoners, review “CHECKLIST: 
Prisoners (HRP-415)” to ensure that you have provided 
sufficient information. 
 
If the research involves persons who have not attained the 
legal age for consent to treatments or procedures involved in 
the research (“children”), review the “CHECKLIST: Children 
(HRP-416)” to ensure that you have provided sufficient 
information. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 31 of 46 
Revised: July 12, 2017 
 
If the research involves cognitively impaired adults, review 
“CHECKLIST: Cognitively Impaired Adults (HRP-417)” to 
ensure that you have provided sufficient information. 
 
Consider if other specifically targeted populations such as 
students, employees of a specific firm or 
educationally/economically disadvantaged persons are 
vulnerable to coercion or undue influence.  The checklists 
listed above for other populations should be used as a guide to 
ensure that you have provided sufficient information.  
N/A 
17.0 Community-Based Participatory Research 
17.1 Describe involvement of the community in the design and conduct of 
the research. 
N/A 
 
Note: “Community-based Participatory Research” is a collaborative 
approach to research that equitably involves all partners in the 
research process and recognizes the unique strengths that each 
brings. Community-based Participatory Research begins with a 
research topic of importance to the community, has the aim of 
combining knowledge with action and achieving social change to 
improve health outcomes and eliminate health disparities. 
18.0 Sharing of Results with Subjects 
18.1 Describe whether or not results (study results or individual subject 
results, such as results of investigational diagnostic tests, genetic 
tests, or incidental findings) will be shared with subjects or others 
(e.g., the subject’s primary care physicians) and if so, describe how 
it will be shared. 
Participants requesting interpretation of neuropsychological tests will be 
scheduled for a clinical consultation and evaluation by Dr. Ralph 
Benedict.  If a patient reports adverse side effects associated withActhar, 
the PI and/or research coordinatorwill notify the patient’s neurologist. 
19.0 Setting 
19.1 Describe the sitesor locations whereyour research team will conduct 
the research. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 32 of 46 
Revised: July 12, 2017 
All research will be conducted through the UBMD Department of 
Neurology located on the fourth floor of the Conventus Building at 1001 
Main St, Buffalo, NY 14203. 
19.2 Identify where your research team will identify and recruit potential 
subjects. 
All identification of potential subjects will be conducted through the 
UBMD Department of Neurology located on the fourth floor of the 
Conventus Building at 1001 Main St, Buffalo, NY 14203, based only on 
clinical referral. During clinic appointments, relapsing patients will be 
assessed (by the treating clinician) for suitability for the study. If deemed 
eligible, and if the patient agrees, the clinician will contact the research 
coordinator with the referral. 
19.3 Identify where research procedures will be performed. 
All research procedures will be conducted in private, noise and 
temperature controlled rooms at UBMD Department of Neurology located 
on the fourth floor of the Conventus Building at 1001 Main St, Buffalo, 
NY 14203. 
19.4 Describe the composition and involvement of any community 
advisory board. 
N/A 
19.5 For research conducted outside of the organization and its affiliates 
describe: 
 Site-specific regulations or customs affecting the research for 
research outside the organization. 
 Local scientific and ethical review structure outside the 
organization. 
N/A 
20.0 Resources Available 
20.1 Describe the qualifications (e.g., training, experience, oversight) of 
you and your staff as required to perform their role. When 
applicable describe their knowledge of the local study sites, culture, 
and society. Provide enough information to convince the IRB that 
you have qualified staff for the proposed research. Note- If you 
specify a person by name, a change to that person will require prior 
approval by the IRB. If you specify people by role (e.g., coordinator, 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 33 of 46 
Revised: July 12, 2017 
research assistant, co-investigator, or pharmacist), a change to that 
person will not usually require prior approval by the IRB, provided 
that person meets the qualifications described to fulfill their roles. 
This study will be conducted and supervised by qualified investigators. 
Dr. Ralph H B Benedict is the senior investigator and a board certified 
neuropsychologist.  He holds the rank of professor in the Department of 
Neurology at the University at Buffalo, State University of New York.  He 
is the lead neuropsychologist for the Jacobs MS Center, directed by 
Bianca Weinstock-Guttman, MD, who is also a contributor to this project.   
All research staff involved in this research project must pass rigorous 
training administering neuropsychological tests, interacting with patients, 
following HIPAA/Good Research practices and guidelines, and obtaining 
informed consent.The study coordinator is responsible for tracking 
referrals, recruitment, screening potential subjects, consenting potential 
subjects, and monitoring patient progress over the course of their 
enrollment.  All research staff has completed CITI and GRP training. 
The PI will be responsible for coordinating the database, conducting 
statistical analyses, coordinating recruitment efforts, and presenting the 
data. 
Describe other resources available to conduct the research: For example, 
as appropriate: 
20.2 Justifythe feasibility of recruiting the required number of suitable 
subjects within the agreed recruitment period.For example, how 
many potential subjects do you have access to? What percentage of 
those potential subjects do you need to recruit? 
On average 120 MS patients per week are seen in the the UBMD 
Department of Neurology located on the fourth floor of the Conventus 
Building at 1001 Main St, Buffalo, NY 14203. Of those, approximately 5-
10 patients are seen for urgent visits related to a relapse or an 
exacerbation. All patients seen by the treating neurologist in this context 
are considered for this study. All patients referred to the research team are 
screened.  
 
20.3 Describe the time that you will devote to conducting and completing 
the research. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 34 of 46 
Revised: July 12, 2017 
One full time research coordinator and two part time research team 
memberswill devote half of their time to conducting and completing the 
research. 
 
20.4 Describe your facilities. 
Our research is conducted at through the UBMD Department of 
Neurology located on the fourth floor of the Conventus Building at 1001 
Main St, Buffalo, NY 14203. All neuropsychological testing will be 
conducted in private, noise and temperature controlled rooms. 
 
20.5 Describe the availability of medical or psychological resources that 
subjects might need as a result of an anticipated consequences of the 
human research. 
Treatment for relapses or other conditions will be used at the discretion of 
the treating clinician as deemed necessary for the management of the 
subject. Participants requesting interpretation of neuropsychological tests 
will be scheduled for a clinical consultation and evaluation by Dr. Ralph 
Benedict.  If a patient reports adverse side effects of Acthar, the PI and/or 
research personnel will notify the patient’s neurologist. 
 
20.6 Describe your process to ensure that all persons assisting with the 
research are adequately informed about the protocol, the research 
procedures, and their duties and functions. 
All new staff will undergo research orientation and will not be cleared for 
research work until approved by the PI and research coordinator.  All new 
staff must complete GRP and CITI training. 
 
21.0 Prior Approvals 
21.1 Describe any approvals that will be obtained prior to commencing 
the research. (E.g., school, external site. funding agency, laboratory, 
radiation safety, or biosafety approval.) 
N/A 
 
22.0 Recruitment Methods 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 35 of 46 
Revised: July 12, 2017 
22.1 Describe when, where, and how potential subjects will be recruited. 
Subjects will be patients from the UBMD Department of 
Neurology/Jacobs MS Center in Buffalo, NY.  Patients deemed eligible 
for the study by their neurologists will be referred to research staff and 
then offered the opportunity to participate in the study.  Research staff will 
then screen patients to determine eligibility for the study. 
 
22.2 Describe the source of subjects. 
Subjects will be patients from the UBMD Department of 
Neurology/JacobsMS Center in Buffalo, NY.   
 
22.3 Describe the methods that will be used to identify potential subjects. 
No advertisements will be used to identify potential subjects; clinician 
referrals will be the only means of identifying potential subjects. 
 
22.4 Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For advertisements, 
attach the final copy of printed advertisements. When advertisements 
are taped for broadcast, attach the final audio/video tape. You may 
submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB 
reviews the final audio/video tape.) 
No advertisements will be used for recruitment of subjects. 
 
22.5 Describe the amount and timing of any payments to subjects. 
Subjects will be given $200 at completion of the study.  At the time of 
consenting, each participant will complete a W-9 form.  Checks and gift 
cards will be mailed from our billing department directly to the 
participant’s address of choice. 
 
23.0 Local Number of Subjects 
23.1 Indicate the total number of subjects to be accrued locally. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 36 of 46 
Revised: July 12, 2017 
We will enroll 30 relapsing-remitting MS patients and 30 stable MS 
patients. 
 
23.2 If applicable, distinguish between the number of subjects who are 
expected to be enrolled and screened, and the number of subjects 
needed to complete the research procedures (i.e., numbers of 
subjects excluding screen failures.) 
During routine clinic appointments, cognitively relapsing patients will be 
assessed (by the treating clinician) for suitability for the study. Subjects 
who agree to participate and pass screening requirements will be enrolled 
in the study.  Thirty relapsing MS patients and 30 stable MS controls will 
be enrolled. 
 
24.0 Confidentiality 
Describe the local procedures for maintenance of confidentiality. 
24.1 Where and how data or specimens will be stored locally? 
Neuropsychological testing data and clinical outcome measures will be 
maintained in de-identified participant charts. These charts will be stored 
in a locked cabinet and entered into a password-protected database. 
Appropriate legal guidelines regarding retention of records will be 
followed. Identifiable data will be destroyed at the earliest possible point. 
The subject will not be identified by name in any study reports, and these 
reports will be used for research purposes only.  Every effort will be made 
to keep the subject’s personal medical data confidential. Stored data will 
be accessed only by the PI and/or designated research staff. The use of 
stored, de-identified data is undetermined at this time. 
 
24.2 How long the data or specimens will be stored locally? 
Data will be stored for the duration of the study and according to federal 
regulations. 
 
24.3 Who will have access to the data or specimens locally? 
PI and research staff. 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 37 of 46 
Revised: July 12, 2017 
24.4 Who is responsible for receipt or transmission of the data or 
specimens locally? 
N/A 
 
24.5 How data and specimens will be transported locally? 
N/A 
 
25.0 Provisions to Protect the Privacy Interests of Subjects 
25.1 Describe the steps that will be taken to protect subjects’ privacy 
interests. “Privacy interest” refers to a person’s desire to place 
limits on whom they interact or whom they provide personal 
information. 
Participants will meet in private interview rooms for in-person 
participation.  When they participate via mail or telephone they are able to 
determine the privacy of the settings in which they participate.   
25.2 Describe what steps you will take to make the subjects feel at ease 
with the research situation in terms of the questions being asked and 
the procedures being performed. “At ease” does not refer to 
physical discomfort, but the sense of intrusiveness a subject might 
experience in response to questions, examinations, and procedures. 
All study participants will be adequately informed of the aims, methods, 
funding sources, anticipated benefits and potential risks of the study.  The 
subject will be informed of the right to abstain or withdraw from 
participation in the study at any time without reprisal.  After ensuring that 
the participant has understood the information, freely given informed 
consent will be obtained. All study procedures, screening, and consenting 
will be conducted in a private, temperature and noise-controlled room. 
 
25.3 Indicate how the research team is permitted to access any sources of 
information about the subjects. 
Only trained and authorized staff will be granted access to data. 
 
26.0 Compensation for Research-Related Injury 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 38 of 46 
Revised: July 12, 2017 
26.1 If the research involves more than Minimal Risk to subjects, describe 
the available compensation in the event of research related injury. 
The University at Buffalo has no program to pay for medical care for 
research-related injury. 
 
26.2 Provide a copy of contract language, if any, relevant to 
compensation for research-related injury. 
N/A 
 
27.0 Economic Burden toSubjects 
27.1 Describe any costs that subjects may be responsible forbecause of 
participation in the research. 
N/A 
 
28.0 Consent Process 
28.1 Indicate whether you will be obtaining consent 
Yes 
 
28.2 Describe where  the consent process take place 
The consent process will take place in a private, temperature and noise 
controlled testing room. 
28.3 Describe any waiting period available between informing the 
prospective subject and obtaining the consent. 
Patient is informed of study procedures when referred to research staff by 
their neurologist.  Consent is obtained prior to any procedures. Participants 
will be provided adequate time and the opportunity to ask questions. 
 
28.4 Describe any process to ensure ongoing consent. 
Subject understanding of study objectives, procedures, potential 
risks/benefits, etc. will be ensured prior to enrollment and at the beginning 
of each subsequent study visit. Assent will be obtained. At each online 
survey assessment patients will be asked to give online consent. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 39 of 46 
Revised: July 12, 2017 
Participant understanding of the procedures, etc. of the study will be 
confirmed during an in-person interface. 
 
28.5 Describe whether you will be following “SOP: Informed Consent 
Process for Research (HRP-090).”If not, describe: 
 
The role of the individuals listed in the application as being 
involved in the consent process. 
 
The time that will be devoted to the consent discussion. 
 
Steps that will be taken to minimize the possibility of coercion 
or undue influence. 
 
Steps that will be taken to ensure the subjects’ understanding. 
We will be following the SOP: Informed Consent Process for Research 
(HRP-090). 
 
Non-English Speaking Subjects 
28.6 Indicate what language(s) other than English are likely to be 
spoken/understood by your prospective study population or their 
legally authorized representatives. 
See Section 3.3 
 
28.7 If subjects who do not speak English will be enrolled, describe the 
process to ensure that the oral and written information provided to 
those subjects will be in that language. Indicate the language that 
will be used by those obtaining consent. 
See Section 3.3 
 
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception) 
28.8 Review the “CHECKLIST: Waiver or Alteration of Consent Process 
(HRP-410)” to ensure you have provided sufficient information for 
the IRB to make these determinations. Provide any additional 
information necessary here: 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 40 of 46 
Revised: July 12, 2017 
Informed consent will be obtained. This research does not involve 
deception. 
 
28.9 If the research involves a waiver the consent process for planned 
emergency research, please review the “CHECKLIST: Waiver of 
Consent for Emergency Research (HRP-419)” to ensure you have 
provided sufficient information for the IRB to make these 
determinations. Provide any additional information necessary here: 
This research does not involve a waiver of consent. 
 
Subjects who are not yet adults (infants, children, teenagers) 
28.10Describe the criteria that will be used to determine whether a 
prospective subject has not attained the legal age for consent to 
treatments or procedures involved in the research under the 
applicable law of the jurisdiction in which the research will be 
conducted. (E.g., individuals under the age of 18 years.)For 
research conducted in NY state, review “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013)” to be aware 
of which individuals in the state meet the definition of “children.” 
N/A 
 
28.11For research conducted outside of NYstate, provide information that 
describes which persons have not attained the legal age for consent 
to treatments or procedures involved the research, under the 
applicable law of the jurisdiction in which research will be 
conducted. One method of obtaining this information is to have a 
legal counsel or authority review your protocol along the definition 
of “children” in “SOP: Legally Authorized Representatives, 
Children, and Guardians (HRP-013).” 
N/A 
 
28.12Describe whether parental permission will be obtained from: 
 
Both parents unless one parent is deceased, unknown, 
incompetent, or not reasonably available, or when only one 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 41 of 46 
Revised: July 12, 2017 
parent has legal responsibility for the care and custody of the 
child. 
 
One parent even if the other parent is alive, known, competent, 
reasonably available, and shares legal responsibility for the 
care and custody of the child. 
N/A 
 
28.13Describe whether permission will be obtained from individuals other 
than parents, and if so, who will be allowed to provide permission. 
Describe the process used to determine these individuals’ authority 
to consent to each child’s general medical care. 
N/A 
 
28.14Indicate whether assent will be obtained from all, some, or none of 
the children. If assent will be obtained from some children, indicate 
which children will be required to assent. 
N/A 
 
28.15When assent of children is obtained describe whether and how it will 
be documented. 
N/A 
 
Cognitively Impaired Adults 
28.16Describe the process to determine whether an individual is capable 
of consent.The IRB sometimes allows the person obtaining assent to 
document assent on the consent document and does not 
automatically require assent documents to be used. 
Individuals are deemed capable of providing consent when they express an 
understanding of the study objectives, procedures, etc. Participants will be 
assessed first by the clinicians during routine clinic visits and then by the 
research coordinator/designated research staff. Understanding of the study 
procedures, objectives, etc. will be determined if the participant is able to 
coherently relay relevant information when asked by the clinician or 
researcher. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 42 of 46 
Revised: July 12, 2017 
Adults Unable to Consent 
When a person is not capable of consent due to cognitive impairment, a 
legally authorized representative should be used to provide consent and, 
where possible, assent of the individual should also be solicited. 
28.17List the individuals from whom permission will be obtained in order 
of priority. (e.g., durable power of attorney for health care, court 
appointed guardian for health care decisions, spouse, and adult 
child.)For research conducted in NY state, review “SOP: Legally 
Authorized Representatives, Children, and Guardians (HRP-013)” 
to be aware of which individuals in the state meet the definition 
of“legally authorized representative.” The list in the consent 
template signature section corresponds to the priority list for NYS.  
Inclusion criteria state that patients must be willing and able to provide 
informed consent. Individuals are deemed capable of providing consent 
when they express an understanding of the study objectives, procedures, 
etc. Participants will be assessed first by the clinicians during routine 
clinic visits and then by the research coordinator/designated research staff. 
Understanding of the study procedures, objectives, etc. will be determined 
if the participant is able to coherently relay relevant information when 
asked by the clinician or researcher.If a participant is cognitively impaired 
to a degree that he/she does not meet the criteria stated above, he/she will 
not be eligible for the study. LARs will not be used.  
 
28.18For research conducted outside of NYstate, provide information that 
describes which individuals are authorized under applicable law to 
consent on behalf of a prospective subject to their participation in 
the procedure(s) involved in thisresearch. One method of obtaining 
this information is to have a legal counsel or authority review your 
protocol along the definition of “legally authorized representative” 
in “SOP: Legally Authorized Representatives, Children, and 
Guardians (HRP-013).” 
N/A 
 
28.19Describe the process for assent of the subjects. Indicate whether: 
 
Assent will be required of all, some, or none of the subjects. If 
some, indicated, which subjects will be required to assent and 
which will not. 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 43 of 46 
Revised: July 12, 2017 
 
If assent will not be obtained from some or all subjects, an 
explanation of why not. 
 
Describe whether assent of the subjects will be documented 
and the process to document assent.The IRB allows the person 
obtaining assent to document assent on the consent document 
and does not routinely require assent documents and does not 
routinely require subjects to sign assent documents. 
N/A 
 
28.20For HUD uses provide a description of how the patient will be 
informed of the potential risks and benefits of the HUD and any 
procedures associated with its use. 
N/A 
 
29.0 Process to Document Consent in Writing 
 
If your research presents no more than minimal risk of harm to subjects and 
involves no procedures for which written documentation of consent is normally 
required outside of the research context, the IRB will generally waive the 
requirement to obtain written documentation of consent. 
(If you will document consent in writing, attach a consent document. If you will 
obtain consent, but not document consent in writing, attach a consent script. 
Review “CHECKLIST: Waiver of Written Documentation of Consent (HRP-411)” 
to ensure that you have provided sufficient information. You may use 
“TEMPLATE CONSENT DOCUMENT (HRP-502)”to create the consent 
document or script.) 
29.1 Describe whether you will be following “SOP: Written 
Documentation of Consent (HRP-091).” If not, describe whether and 
how consent of the subject will be obtained including whether or not 
it will be documented in writing. 
We will be following the SOP: Written Documentation of Consent (HRP-
091). 
 
30.0 Drugs or Devices 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 44 of 46 
Revised: July 12, 2017 
30.1 If the research involves drugs or device, describe your plans to store, 
handle, and administer those drugs or devices so that they will be 
used only on subjects and be used only by authorized investigators. 
Acthar will be provided to the investigators by Questcor and to the 
patients by the investigators. All drug shipments received will be counted 
and recorded in a drug accountability binder maintained by the study 
coordinator.  Copies of the receipt of the study drugs as shipped will be 
kept in the binder.  Study drug will be stored in accordance with 
guidelines provided by Mallinckrodt (formerly Questcor).  Study 
medication will be supplied to patients by trained clinical staff under the 
supervision of the investigators and self-administration instructions 
provided verbally and in-writing.  Patients will receive sufficient supply of 
Acthar as prescribed by the investigator (Bianca Weinstock-Guttman, 
MD), in accordance with the treatment protocol and clinical judgment.  
Drugs destroyed or accidentally discarded will be accounted for.  Unused 
portions of Acthar will be returned to the investigators following the 
treatment period and disposed of in accordance with guidelines provided 
by Mallinckrodt (formerly Questcor).   
 
If the drug is investigational (has an IND) or the device has an IDE or a 
claim of abbreviated IDE (non-significant risk device), include the 
following information: 
30.2 Identify the holder of the IND/IDE/Abbreviated IDE. 
N/A 
 
30.3 Explain procedures followed to comply with FDA sponsor 
requirements for the following: 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 45 of 46 
Revised: July 12, 2017 
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated 
IDE studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
Response:N/A 
 
 
 


 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: Effects of adrenocorticotropic hormone (Acthar gel®) on recovery 
from cognitive relapses in MS. 
 
 
Page 46 of 46 
Revised: July 12, 2017 
 

ICF_001.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Effects of Acthar on Recovery From Cognitive Relapses in MS 
NCT02290444 
Informed Consent Form 
Document Revision Date: June 12, 2018 
IRB Approval of Revision: July 30, 2018 


Permission to Take Part in a Human Research Study
Page 1 of 8
IRB ApprovalPeriod
HRPP Revision Date: May 13, 2015
University at Buffalo Institutional Review Board (UBIRB)
Office of Research Compliance | Clinical and Translational Research Center Room 5018
875 Ellicott St. | Buffalo, NY 14203
UB Federalwide Assurance ID#: FWA00008824
Adult Consent to Participate in a Research Study
Title of research study: Effects of Adrenocorticotropic Hormone (Acthar®) on Recovery from 
Cognitive Relapses in MS
Version Date: 12 June 2018
Investigator: Ralph Benedict PhD
Why am I being invited to take part in a research study?
You are being invited to take part in a research study because you are either: 1) having an MS relapse 
and your doctor or nurse practitioner feels that you may benefit from Acthar (Adrenocorticotropic 
Hormone) treatment, or 2) your MS is stable and you are matched on demographic variables to a 
relapsing participant.  
What should I know about a research study?

Someone will explain this research study to you.

Whether or not you take part is up to you.

You can choose not to take part.

You can agree to take part and later change your mind.

Your decision will not be held against you.

You can ask all the questions you want before you decide.
Who can I talk to?
If you have questions, concerns, or complaints, or think the research has hurt you, talk to the research 
team at 716-323-0552. You may also contact the principle investigator, Dr. Ralph Benedict at 716-
323-0556.You may also contact the research participant advocate at 716-888-4845 or 
researchadvocate@buffalo.edu. 
This research has been reviewed and approved by an Institutional Review Board (“IRB”). You may 
talk to them at (716) 888-4888 or ub-irb@buffalo.edu if:

You have questions about your rights as a participant in this research

Your questions, concerns, or complaints are not being answered by the research team.

You cannot reach the research team.

You want to talk to someone besides the research team.

You want to get information or provide input about this research.
IRB Approval Period:  
7/20/2018 - 8/6/2018  


Permission to Take Part in a Human Research Study
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IRB ApprovalPeriod
HRPP Revision Date: May 13, 2015
Why is this research being done?
The purpose of this study is to evaluate the effect of a medication called Acthar® (Adrenocorticotropic 
hormone) on people with multiple sclerosis (MS) who experience a relapse (exacerbation) that affects 
their cognition. The study drug is investigational in so far that its effect on cognition is unknown.  This 
type of relapse may affect concentration, memory, or level of fatigue, symptoms that are in general less 
carefully evaluated as compared to the physical limitations that usually are much easier identified 
during an acute MS relapse.
How long will the research last?
We expect that you will be in this research study for 90 days.
How many people will be studied?
We will enroll 30 relapsing MS patients and 30 stable MS patients matched on demographic variables.  
What happens if I say yes, I want to be in this research?
You will be asked to make a total of two (2) visits, approximately 90 days apart. Each visit will 
involve: a physical/neurological exam, neuro-performance testing, and self-report questionnaires. Each 
study visit is expected to take approximately 60 minutes. 
During the first visit:
1) Your medical history and medications will be reviewed and you will be given a neurological 
examination, if one has not already been completed in the past 7 days.  
2) You will complete a brief test of cognition.
3) If you meet the criteria required for the study and you wish to continue, you will complete a series 
of tests and questionnaires that measure your walking speed, dexterity, memory and thinking speed.
4) If you are in the treatment group (relapsing), you will be instructed on self-administration of 
Acthar®(Adrenocorticotropic Hormone)  and receive your first dose. You will be given instructions on 
how much Acthar® to take and for how many days to take it at home. The study drug will be provided 
to you through the study. If you are stable and matched to another participant, there will be no changes 
in your treatment or clinical care. 
5) You will be contacted 7 days, 30 days, and 90 days from your first visit and asked about changes in 
your medical status or medications.
At 90 days, you will return for the 60-minute follow-up visit where you will receive a neurological 
examination and complete the cognitive testing and questionnaires, again.
Some of the surveys have forms are to be completed by a person who knows you well, such as a 
spouse, adult child or a caregiver. If such a person is available and has agreed to help you participate in 
this study, that person will also provide information about you using the surveys and this will require 
about 15 minutes of their time. If that individual is not available in person, then with your permission, 
we will contact him/her by telephone.
By signing this consent, you are giving us permission to access the clinical data collected during your 
initial clinical visit and screening tests for eligibility to take Acthar (Adrenocorticotropic Hormone). 
IRB Approval Period:  
7/20/2018 - 8/6/2018  


Permission to Take Part in a Human Research Study
Page 3 of 8
IRB ApprovalPeriod
HRPP Revision Date: May 13, 2015
What are my responsibilities if I take part in this research?
If you take part in this research, you will be asked to provide informed consent and to complete study 
visits at days 0 and 90. If you are a relapsing patient you will be required to take the appropriate doses 
of Acthar (Adrenocorticotropic Hormone) in accordance with the study and your neurologist’s 
recommendation.
What happens if I do not want to be in this research?
Participation in this study is voluntary. You may refuse to participate without penalty and such 
refusal will not prejudice future treatment at the Jacobs MS Center. If you choose to withdraw 
from the study, the data collected up to the time of withdrawal will continue to be used, but you 
will no longer be contacted and no further data will be collected.
What happens if I say yes, but I change my mind later?
You can leave the research at any time; it will not be held against you. Your participation in this study 
is voluntary.  Your refusal to participate will not prejudice your future treatment or benefits. You are 
free to discontinue participation in the study at any time without fear of penalty or loss of medical care 
or loss of any benefits to which you may otherwise be entitled. If you choose to withdraw from this 
study, or if the investigator withdraws you from the study, no further information will be collected 
from you or about you. You should know, however, that the information collected about you up to the 
time of your withdrawal may continue to be used. 
Is there any way being in this study could be bad for me?
There are no foreseeable risks associated with the neurological testing.  It is possible that you may 
become fatigued and/or feel uncomfortable answering questions in the neuropsychological, or 
vocational examinations.  If so, you can stop, or decline to answer at any time.
The side effects that may occur with Acthar® (Adrenocorticotropic Hormone) are related primarily to 
its steroid-like effects similar to IV Solumedrol (Methylprednisolone).  There may be increased 
susceptibility to new infection and increased risk of reactivation of latent infections.  
Acthar® (Adrenocorticotropic Hormone) may cause various side effects such as:

Dizziness

Nausea

Anaphylactic or hypersensitivity reactions

Hypertension (high blood pressure)

Congestive heart failure

Thin, fragile skin

Erythema (redness of the skin)

Increased sweating

Increased requirements for insulin or oral hypoglycemic (low blood sugar) agents in diabetics

Elevated blood sugar

Cushing’s syndrome
IRB Approval Period:  
7/20/2018 - 8/6/2018  


Permission to Take Part in a Human Research Study
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IRB ApprovalPeriod
HRPP Revision Date: May 13, 2015

Gastrointestinal perforation and bleeding or peptic ulcer

Pancreatitis (inflammation of the pancreas)

Abdominal distension (enlargement)

Water retention

Peripheral edema (swelling of the extremities)

Headache

Impaired wound healing

Ecchymosis (bruising)

Menstrual irregularities

Loss of muscle mass

Thinning of the bones

Cataracts

Glaucoma

Onset or worsening of euphoria, insomnia, irritability, mood swings, personality changes, 
depression, anxiety and psychosis

Fatigue

Injection site pain
Pregnancy
Acthar® (Adrenocorticotropic Hormone) may hurt a pregnancy or fetus in ways that are unknown. These 
may be a minor inconvenience or may be so severe as to cause death. You should not be or become 
pregnant while in this research study. If you become pregnant, continuing the study drug may not be safe 
for your unborn baby and for yourself.  Therefore, you must report the pregnancy immediately to the 
site’s staff and your participation in the study will be stopped. 
Other Risks:
There may be other side effects, which are unknown at this time.
As with all other medications, you should be aware that you may develop some side effects to the 
study drug. You will be watched carefully for any side effects and you must report changes in your 
condition to your study physician.
Will being in this study help me in any way?
You may or may not have any direct benefit by participating in this research.  This study is designed to 
learn more about Acthar® (Adrenocorticotropic Hormone). The study results may be used to help other 
patients in the future. Results of the Neuropsychological testing will be available upon request.
What happens to the information collected for the research?
Efforts will be made to limit the use and disclosure of your personal information, including research 
study and medical or education records, to people who have a need to review this information. We 
cannot promise complete secrecy. Organizations that may inspect and copy your information include 
the IRB and other representatives of this organization.
IRB Approval Period:  
7/20/2018 - 8/6/2018  


Permission to Take Part in a Human Research Study
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HRPP Revision Date: May 13, 2015
The sponsor, monitors, auditors, the IRB, and the Food and Drug Administration will be granted direct 
access to your medical records to conduct and oversee the research. By signing this document, you are 
authorizing this access. We may publish the results of this research. However, we will keep your name 
and other identifying information confidential.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.
Federal law provides additional protections of your medical records and related health information. 
These are described in the HIPAA section of this document.
Can I be removed from the research without my OK?
The principal investigator of the study can remove you from the research study without your approval 
upon your neurologist’s request. Circumstances that could possibly lead to your withdrawal would be 
if continuation of treatment with Acthar is no longer in your best interest, based on your treating 
clinician’s judgment. Your treating clinician may remove you from the study at any time should he/she 
feel it is no longer in your best interest.
We will tell you about any new information that may affect your health, welfare, or choice to stay in 
the research. 
What else do I need to know?
This research study is being funded by Mallinckrodt (formerly Questcor) Pharmaceuticals. Acthar 
(Adrenocorticotropic Hormone) will be provided to you through the study. 
If you need medical care because of taking part in this research study, contact the investigator and 
medical care will be made available. Generally, this care will be billed to you, your insurance or other 
third party.  The Research Foundation of SUNY Buffalo has no program to pay for medical care for 
research-related injury.
If you agree to take part in this research study, we will pay you $200 for your time and effort. 
HIPAA:  Authorization for the Use and Disclosure of Identifiable Health 
Information for Research Purposes
This section describes information about you and about your health that will be obtained by the 
researchers when you participate in the research study. Health information is considered 
"protected health information" when it may directly identify you as an individual. By signing this 
form, you are agreeing to permit the researchers and/or other parties (described in detail below) to 
have access to this information. If there are any parts of this form that you do not understand, 
please be sure to ask us for further clarification.
A. What protected health information will be collected about you as part of this research 
study?
IRB Approval Period:  
7/20/2018 - 8/6/2018  


Permission to Take Part in a Human Research Study
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X  Information from your full medical records:
X  New Health Information created from study related tests, procedures, visits, and/or   
questionnaires as described in this consent form.
Provide a general description of information that will be collected: 
We will collect information on your disease course and MS symptoms, medications, physical 
and neurological testing data. 
B.    Who is authorized to provide or collect this information?
X Principal Investigator or designee
C.   With whom may your protected health information be shared? 
Your health information may be shared with others outside of the research group for purposes 
directly related to the conduct of this research study or as required by law, including but not 
limited to:
X
Clinical staff not involved in this research study who may become involved in your 
care if it is potentially relevant to your treatment
X
The sponsor of this research study is Mallinckrodt (formerly Questcor) 
Pharmaceuticals.
X 
This research is being conducted in association with the Research Foundation of 
SUNY Buffalo.
Your information may also be shared with individuals or entities responsible for general 
administration, oversight and compliance of research activities. Examples of this include the 
institution's Privacy and Security Officers or other internal oversight staff, Safety Monitoring 
Boards, an Institutional Review Board, The Research Foundation of the State University of 
New York, University at Buffalo Foundation Services, and accrediting bodies, or with certain 
government oversight agencies that have authority over the research including the Department 
of Health and Human Services (HHS), the Food and Drug Administration (FDA), the National 
Institutes of Health (NIH), and the Office of Human Research Protections (OHRP). Your 
information may also be shared with other entities as permitted or required by law. All 
reasonable efforts will be used to protect the confidentiality of your individually identifiable 
health information that may be shared with others as described above.
All reasonable efforts will be used to protect the confidentiality of your protected health 
information. There is the potential for individually identifiable information and the associated 
health information obtained with this authorization to be re-disclosed by the recipient(s). After 
such a disclosure, the information may no longer be protected by the terms of this authorization 
against further re-disclosure.
D.  How long will this information be kept by the Principal Investigator?
IRB Approval Period:  
7/20/2018 - 8/6/2018  


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IRB ApprovalPeriod
HRPP Revision Date: May 13, 2015
X  This authorization has no expiration date. The researchers may continue to rely on this 
authorization to obtain and use protected health information about you unless you 
revoke this authorization in writing.
    X   
Your protected health information will go into a database that will be maintained 
indefinitely. Any future study using this information that falls outside the scope of 
this current study will be required to follow guidelines designed to govern access to 
that information and to protect the privacy of that information.
E.  What are your rights after signing this authorization?
You have the right to revoke this authorization at any time. If you withdraw your authorization, 
no additional efforts to collect individually identifiable health information about you will be 
made. You should know, however, that protected health information acquired using this 
authorization prior to its withdrawal may continue to be used to the extent that the 
investigator(s) have already relied on your permission to conduct the research. If you chose to 
withdraw this authorization, you must do so in writing to the following individual(s):
Ralph Benedict, PhD
UBMD Neurology
Conventus Medical Center
1001 Main St,
Fourth Floor
Buffalo, NY 14203
If you send us a request to withdraw your authorization, we will forward that request to the 
institutions we have shared it with in order to collect your individually identifiable health 
information. 
F.  What will happen if you decide not to sign this authorization?
Refusing to sign this authorization will not affect the present or future care you receive at this 
institution and will not cause any penalty or loss of benefits to which you are otherwise entitled. If you 
decide not to sign this authorization, you will not be able to participate in the research study.
IRB Approval Period:  
7/20/2018 - 8/6/2018  


Permission to Take Part in a Human Research Study
Page 8 of 8
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HRPP Revision Date: May 13, 2015
Signature Block for Capable Adult
Your signature documents your permission to take part in this research. By signing this form, you 
are not waiving any of your legal rights, including the right to seek compensation for injury related 
to negligence or misconduct of those involved in the research.
Signature of subject
Date
Printed name of subject
Signature of person obtaining consent
Date
Printed name of person obtaining consent
IRB Approval Period:  
7/20/2018 - 8/6/2018