Comparison of Posterior Cellular Bonegraft Options for Single Level Lumbar Spinal Fusion: A Randomized Trial
Phase: PHASE2
Conditions: Disc Degenerative Disease, Spine Fusion for Degenerative Spine Disease
Sponsor: Midwest Spine & Brain Institute

 
 
 
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NCT07187362 
 
Study Protocol Document Date: October 3, 2015 
 
Title 
Stem cell containing bone graft options and bone morphogenetic protein (BMP) compared to iliac 
autograft for single level posterior spinal fusion 

 
 
 
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RESEARCH/PROJECT REVIEW APPLICATION 
This form fulfills both Research and IRB requirements for HealthEast.  Please 
complete all questions, even if you are not applying for IRB approval. 
1 Project Title:  
Bone graft options for single level posterior spinal fusion 
2 Contact Information  
a. Principal Investigator(s): Glenn Buttermann, MD 
Mailing Address: 1950 Curve Crest Blvd., Stillwater, MN  55082 
Telephone: 651-430-3800 
FAX: 651-653-4844 
Email: butte011@umn.edu 
Please indicate the training or education completed in the protection of human subjects (this is 
required):  
CITI Human Subjects Research Curriculum 
b. Co- Investigator(s): 
Mailing Address: 
Telephone: 
FAX: 
Email: 
Indicate the training and education completed in the protection of human subjects (this is optional): 
c. Research Staff (personnel you wish to include in correspondence related to this study, e.g. 
study coordinators): 
Mailing Address: 
Telephone: 
FAX: 
Email: 
 
3 Abstract (500 words or less, do not refer to "see protocol" for abstract): 
This abstract should consist of two paragraphs, written in lay language, labeled 
Background and Methods. They should briefly describe the problem being 
addressed in the study, including the hypothesis or study question and how the 
study will be performed. 
Background. Achieving spinal fusion requires bone graft and is most reliable using 
an anterior/posterior technique. The bone graft is placed between the vertebral 
bodies during the anterior fusion and placed in and adjacent to the facet joints for the 
posterior fusion. Because there is greater bony surface area between the vertebral 
__ HMRI 
__ HealthEast  
__ Non HealthEast 

 
 
 
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bodies, this area has a more reliable fusion success rate. Instrumentation which 
helps stabilize the vertebra during the healing period also increases the fusion rate.  
The bone graft for the posterior fusion may come from a variety of sources. 
Historically, bone graft was obtained from the iliac portion of the patient own pelvis, 
IBG, but this resulted in additional postoperative pain (sometimes worse than the 
fusion wound). Alternatives are currently the most common form of bone graft, but 
there is very little knowledge as to the superiority of one alternative over another. 
The purpose of this research is to determine the ability to achieve a solid posterior 
spinal fusion using sources to bone graft coming from the patient’s own iliac crest, or 
from bone morphogenic protein (BMP), which is costly, but known to give very high 
fusion rates when applied anteriorly, or from donor bone combined with stem cells 
derived from either donor bone, fat, or amniotic membrane/fluid (placenta or 
“afterbirth” tissue). 
 
Methods. Patients who are surgical candidates for a one-level anterior/posterior 
lumbar fusion will be randomized to IBG or one of 4 types of bone graft alternatives 
(small Medtronic Infuse BMP, Orthofix Trinity allograft bone marrow derived stem 
cells combined with morcelized cancellous allograft, Allosource Allostem fat derived 
stem cells combined with morcelized cancellous allograft, or Nutech Nucel amnion 
derived stem cells combined with morcelized cancellous allograft). There will be 20 
patients in each group. All anterior fusions will use BMP; the study only applies to 
the posterior fusion. Neither patient nor surgeon is blinded to the posterior type of 
bone graft. The volume of bone graft is the same for each type, approximately 5cc. 
The decortication part of the fusion is identical for all patients, as is the type of 
instrumentation (anterior plate and posterior facet screws). Limited CT scans of the 
fusion will be obtained at approximately one year postoperatively to assess fusion 
success of both anterior and posterior regions. The limited CT scan results in 
approximately 2.88 mSv radiation exposure, or similar to one year’s worth of 
background radiation. Secondary endpoints are patient outcomes for pain and 
function using standard VAS pain scales and Oswestry. Disability Index at one year 
postoperatively will be assessed to ascertain the relationship between clinical 
success and fusion success since prior studies suggest that success is only related 
to the status of anterior fusion. 
 
4 Study Design/Protocol (Please answer the questions below and attach the study 
protocol): 
a. What are the objectives of the proposed research/project? 
Evaluate the effectiveness of 5 types of bone graft material in obtaining a solid 
posterior fusion for one level anterior/posterior lumbar spinal fusion. 
b. What is the significance of the proposed study? (Provide the context for the 
study, and the rationale.  What is known about the topic?  Why is the study 
important?  What kind of answers will the study provide)? 

 
 
 
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Iliac bone autograft is an additional procedure with known morbidity and high rate 
of residual pain postoperatively at the graft donor site leading to reduced 
outcomes. Bone morphogenic protein is effective in obtaining fusion but is used 
off label, has multiple side effects, and is expensive to hospital systems. Stem 
cell bone products are an attractive alternative that avoids pain related to the 
graft donor site and have a far better safety profile than BMP. 
• What will subjects be asked to do? 
Patients who are scheduled to undergo a single level lumbar anterior/posterior 
spinal fusion with instrumentation will be eligible to participate. Subjects will be 
asked to agree to be randomized to one of five types of bone graft for the 
posterior portion of their fusion surgery. 
• What is the study design? 
Prospective, non-blinded, randomized study design of 5 types of bone graft 
material applied to 100 patients (20 patients per group). 
c. Describe the proposed data collection procedures.  Attach any forms such as 
surveys, chart abstraction or other data collection forms. 
Data collection includes age, date of surgery, date of follow-up CT scan (>9 
months postop), assessment of fusion at follow-up, smoking and osteoporosis 
status (which may affect fusion status), type of bone graft used for the anterior 
procedure (all will be bone morphogenic protein combined with local autograft), 
type of bone graft used for the posterior procedure.  
d. List the routine medical related costs for this research/project/trial. 
1) ROUTINE OR STANDARD MEDICAL CARE:  This includes items or services that 
are typically provided absent a clinical trial and those required for the 
provision of the investigational item or service, as well as appropriate 
monitoring, prevention of complications, and the diagnosis or treatment of 
complications arising from the provision of an investigational item or 
service. 
The fusion surgery is considered standard of care. The costs of a single 
level lumbar fusion is information known to HealthEast as they are the 
entity that charges for this type of surgery. The charges and 
reimbursement for spinal surgery at HealthEast has not been shared with 
the investigator. 
2) STUDY RELATED CARE:  List the additional items or services required for the 
provision of the investigational item or service 
Additional items related to cost are limited CT scan at >9months 
postoperatively. This cost is $265 per patient and will be paid for by the 
principal investigator/Midwest Spine & Brain Institute.  

 
 
 
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3) STUDY SPECIFIC CARE:  List items or services furnished solely to satisfy data 
collection, analysis needs, or to determine trial eligibility. 
 
Data will be collected by the PI on a personal password protected laptop 
computer. Statistical analysis will be obtained from a third party. 
 

 
 
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5 Financial Information 
a. Will this project by funded by, or supported by a center or cooperative group(s) that is 
funded by NIH, CDC, AHRQ, HCFA, or the VA? 
 
 
   NO 
   YES - Specify: 
b. Will this project be funded through other outside granting agencies? 
If yes, please list. 
 
   NO 
   YES - Source(s): 
c. Do any of the investigators have a financial interest with the funding source/study 
sponsor, and if so, what type (e.g. shareholder, stock options, paid consultant or medical 
director, travel expense reimbursement, provision of office supplies or equipment)? 
 
   NO 
   YES - What Type? 
d. Does this study have an IND number? 
 
   NO 
   YES -   Number: 
e. Does this study have an IDE number? 
 
 
   NO 
   YES -   Number: 
f. 
Is this trial exempt from having an IND under 21 CFR 312.2(b)(1)? 
 
 
   NO 
   YES 
   NA 
g. Inclusive Date of Project: 
Start Date: October 1, 2015   End Date: January 1, 2020 
h. Aspects of this study involving the use of human subjects will be conducted in: 
 
 Hospital 
 Physician's Office/Clinic 
 Other (please identify): 
6 Subject Population 
a. Check all that apply: 
 Inpatient 
 Outpatient 
 Healthy Volunteers  
 Other 
b. Describe criteria for inclusion and exclusion of subjects in this study: 
- 
Inclusion Criteria:  
Lumbar spinal fusion of a single segment for a degenerative condition; age 18 – 
65 
- 
Exclusion Criteria: 
Prior lumbar fusion surgery; prior abdominal surgery precluding access to the 
anterior spine; lytic spondylolisthesis; high grade stenosis requiring partial or 
complete facetectomy 
c. If the study includes use of clinical patients, will approval be obtained from the attending 
M.D.? 
 
   NO 
   YES -   Describe how: 

 
 
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Consent will be obtained at the time of preoperative discussion in patients who desire to 
proceed with fusion surgery after having failed non-operative treatment for their 
degenerative condition. Risk and benefits of surgery as well as specific risks related to 
bone graft products will be presented. 
d. How many subjects do you plan to enroll? 
100 
e. Please indicate the approximate number of subjects to be enrolled for each gender 
category: 
 40 Male 
60 Female 
f. 
Expected Age Range-please check all that apply: 
 0-7 (include parental consent form) 
 8-17 (include parental consent form and child assent form) 
 18-65 
 65 and older 
Exact ages to be included:18-65 
g. Protected Populations to be Studied-please check all that apply 
 Pregnant women 
 Embryos/Fetuses 
 Prisoners 
 Minors (under age 18) 
 Mentally/Emotionally/Developmentally Disabled Persons 
 NA   
 
h. If this is a multi-center study, what is the total number of subjects to be enrolled from all 
centers: 
NA 
 
i. 
How will subjects be chosen? (e.g. records, classes, referral)  
Patients who are followed and treated for their spinal condition and who meet the entry 
criteria will be enrolled from the PI’s clinical practice. 
j. 
Will subjects receive any inducements or rewards for participating in the study? 
 
   NO 
   YES - Please explain: 

 
 
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k. Will subjects be charged for any research-related procedures? 
 
   NO 
   YES -   If amount is known, please list: 
 
 
 
 

 
 
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7 Risk 
The purpose of this section is to determine whether the human subjects involved in the 
proposed research project will be placed at risk. In order to help determine what risk 
subjects will be exposed to, please answer the following questions: 
 
DOES THE RESEARCH PLAN IN THIS PROJECT INVOLVE: 
YES 
NO 
a. Possible invasion of privacy of subject or family, including use of personal 
information or records? .................................................................................. 
 ...........
 
b. The administration of physical stimuli other than auditory and visual 
stimuli associated with normal classroom situation?  ..................................... 
 ...........
 
c. Deprivation of physiological requirements such as nutrition or sleep; 
manipulation of psychological and/or social variables (e.g. sensory 
deprivation, social isolation, psychological stresses, etc.)?  ........................... 
 ...........
 
d. Any probing for information in survey or interview that an individual might 
consider to be personal or sensitive? ............................................................ 
 ...........
 
e. The requirement of physical exertion beyond normal classroom 
situations?  .................................................................................................... 
 ...........
 
f. 
The presentation to the subject of any materials which they might find to 
be offensive, threatening or degrading?  ........................................................ 
 ...........
 
g. Deception as part of the experimental procedure? If the study involves the 
use of deception, the protocol must include a description of this fact and 
the "debriefing procedure" which will be used upon completion of the 
study. ............................................................................................................ 
 ...........
 
h. The use of drugs? If yes, please comment on the preparation, dosage, 
toxicity, significant side effects, etc.  .............................................................. 
 ...........
 
i. 
Any surgical processes? ................................................................................ 
 ...........
 
j. 
Administration of approved/unapproved devices? ......................................... 
 ...........
 
k. Blood drawing, marrow biopsy sampling, biopsy of other tissues, etc (if 
“yes”, state the amount (volume measure) and frequency at which samples are 
taken. The consent form must include lay term equivalents for the amount, e.g. 
teaspoons. Please distinguish between procedures that are diagnostic from 
procedures performed solely for research ........................................................... 
 ...........
 
l. 
The use of radioisotopes, or other sources of ionizing radiation including 
X-rays? .  ....................................................................................................... 
 ...........
 
m. Use of controlled substances? ....................................................................... 
 ...........
 
n. Describe the nature and degree of risk or harm checked above: 
The risks associated with obtaining iliac bone autograft and include pain, 
infection (<5%), pelvic fracture (very rare). 

 
 
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The limited post-procedure CT scan results in approximately 2.88mSv of 
radiation exposure, which is equivalent to one year’s worth of background 
radiation. 
o. List any anticipated direct and/or societal benefits to participating in this 
research project. If none, state that fact here and in the consent form:  
The benefits are for future spinal fusion patients who may be able to 
avoid the morbidity related to harvesting iliac bone autograft yet still 
reliably obtain a solid posterior fusion using one of the alternative bone 
graft products evaluated in this study. 
p. Do the benefits of this study outweigh the risks? .................................. Yes 
 No 
 
8 Confidentiality of Data 
a. Will any data from this study be a part of permanent record (identifiable to the subject) 
that will be made available to physician, employer, supervisor, student, FDA, etc.? 
 
   NO 
   YES - Please explain: 
Both the patient and their physician can access their medical record including the 
operative report which indicates the type of bone graft used in their fusion. 
b. Where, how long, and in what format (paper, electronic, digital) will the data be kept?  
The data will be kept electronically for approximately 10 years. 
c. Describe what security precautions (locked cabinet, password protected, encryption, 
etc.) that will be taken to protect the data.  
The data will be stored on a password protected computer. 
9 Informed Consent 
 
Informed consent is necessary for all research and other activities which involve humans as 
subjects. It may be secured in several ways, but usually must be documented in some 
manner. The investigator may determine what method he/she believes would best serve the 
interest of the subject population. However, the Committee reserves the right, upon review 
of the research and its attendant risks, to require alternate and/or more stringent means of 
securing consent. Use of subjects not able to give personal consent for reason of age, 
mental status, legal or other such status, require that consent be secured from the 
parents(s) or legal guardian. If it appears necessary to use consent procedures which differ 
from those normally required, please define and justify their use. 
At the top of the Informed Consent form, the study/trial name, the sponsor of the 
study, and the sponsor-assigned protocol number MUST be clearly identified. 
In addition, the section on the Informed Consent dealing with problems, 
questions, etc., must include the following statement:  
 
"You may also contact Dean Huska, Chair, HealthEast Institutional Review 
Board (651-232-3234 or dhuska@HealthEast.org) with questions regarding your 
rights as a patient in research studies". 
The Informed Consent must also document the individual who reviewed the 
informed consent with the subject. 

 
 
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I confirm that I have personally explained the nature, purpose, duration, and 
foreseeable benefits and risks of the trial to the participant (or if applicable, the 
participant’s legal representative) named above. 
 
_________________________________ 
 
Person who administered the consent 
 
_________________________________ 
________________________ 
 
Signature 
Date 
Please describe procedures used to obtain informed consent and attach a copy of the 
informed consent document. These procedures should include an explanation of the 
following: 
a. In relation to actual data gathering, when will consent be discussed and documentation 
obtained? 
Consent for this study will be reviewed, discussed, and obtained from the patient 
preoperatively. The assessment of fusion status occurs post-operatively. 
Will the investigator(s) be securing all informed consent? 
 Yes  
 No – If no, please list the name(s) job title(s) and credentials of the 
individual(s) responsible for obtaining informed consent  
b. What is the reading level of the informed consent? How was this level measured?  
10th grade-Flesch-Kincaid readability statistics 
*Please be prepared to discuss with the Institutional Review Board how you and/or your 
research team will assure subjects’ understanding of the consent process. 
You may refer to the HealthEast consent template (Appendix A) when drafting the informed 
consent document. Do not submit sponsored prepared consent forms without editing the 
form to include HealthEast IRB standard language and all essential elements of informed 
consent. 
Under specific conditions, when justifiable, documentation of informed consent can be 
waived or altered. These limited conditions are described in 45CRF46.116 and 45 CRF 
46.117. If you believe that this research qualifies for waived or altered consent, please 
complete Appendix B and include this form with the completed application. 

 
 
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10 VERIFICATION OF APPLICATION 
 
I certify that the information furnished concerning the procedures to be taken for the 
protection of human subjects is correct. I will seek to obtain prior approval for any 
substantive modification to the proposal and will report promptly any unexpected or 
otherwise significant adverse effect in the course of the study 
 
 
 
 
 
 
 
 
______________________________ 
Signature of Principal Investigator 
 
Date 
 
 
 
11 How will the proposed research protocol impact HealthEast facilities, staff, or 
resources? (Provide assessment of the project’s impact to resources and staff 
workload by answering the following questions.) 
a. Will this project require additional resources from HealthEast? 
 
   NO 
   YES -  Specify: 
b. Will this project increase the staff workload? 
 
   NO 
   YES -  Specify: 
 
12 How will the results of the study be reported?  Who will the results be reported 
to?  
Study results may be presented at a spine conference or in a peer-reviewed 
professional journal.  
 
13 Budget:  Attach a budget.  If applicable, also include a detailed list of medical 
related services/procedures and associated costs for this research/project/trial (as 
outlined on Question 4d).  
The only study-related cost is the follow-up CT scan, which will be paid for by the 
principal investigator/Midwest Spine & Brain Institute. 
You have reached the end of this form. Please make sure that you have responded to every 
question on this application, even if your response is “not applicable”.