Clinical trial NCT02739035
Conditions: Stiffness Following Total Knee Arthroplasty
Sponsor: Mayo Clinic
Start date: 2016-04-01; Completion date: 2022-12-01
Enrollment: 130 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Compare the outcome following manipulation under anesthesia for stiffness in a randomized controlled fashion with one group receiving IV dexamethasone and oral celecoxib at the time of manipulation to a control group receiving manipulation alone.

Outcomes will include pain, range of motion, as well as subjective outcome scores.

Detailed description:
Stiffness is a potential complication following Total Knee Arthroplasty (TKA). While a variety of factors have been cited as possible causes, such as component malrotation or improper soft-tissue balancing, however, an etiology is not always appreciated. Histologic and arthroscopic evidence of fibrosis suggests that an inflammatory process may contribute to loss of knee range of motion following surgery. Manipulation under anesthesia remains standard of care for stiffness following TKA. Manipulation shows improved range of motion for stiffness after total knee arthroplasty, however, patients do not always achieve full range of motion. Furthermore, repeat manipulation and manipulation greater than 8 weeks post-surgically have shown limited improvements. Given a possible role of the host inflammatory response and the importance of early gains in knee range of motion following total knee arthroplasty, limiting the inflammatory response at the time of manipulation may improve outcomes. Investigators would like to assess the role of anti-inflammatory medications to optimize range of motion and outcome for manipulation under anesthesia for stiffness following TKA.

Arms: arm 1: Subjects will be given manipulation under anesthesia, will fill out questionnaires about their knee and quality of life and will be followed throughout their routine follow up to assess their continued process. Subjects will fill out questionnaires at the time of their consent and their 6-week and 1-year follow up visits. The questionnaires will take about 15-20 minutes to complete. arm 2: For subjects assigned to the MUA with anti-inflammatory medication group, an intravenous (into the vein) dose of dexamethasone will be given at the time of MUA. Subjects in this group will also receive celecoxib. They will be asked to take the medicine one time daily either at morning or night time with food and water for 2 weeks following MUA. Subjects will also be followed throughout their routine follow up to assess their continued process, and they will fill out questionnaires at the time of their consent and their 6-week and 1-year follow up visits. The questionnaires will take about 15-20 minutes to complete.
Interventions: intervention 1: Dexamethasone intervention 2: Celecoxib
Intervention descriptions: intervention 1: 8 mg of IV dexamethasone immediately before MUA. intervention 2: 2 weeks per mouth of celecoxib (200 mg daily)

Protocol documents:
Prot_SAP_000.pdf: 
 June 8, 2018 
 
Version 6 
 
1
 
1 
 
2 
Manipulation Under Anesthesia (MUA) to Treat Postoperative 
3 
Stiffness after Total Knee Arthroplasty: 
4 
A Multicenter Randomized Clinical Trial 
5 
 
6 
 
7 
Matthew P. Abdel, M.D.  
8 
Paul Sousa, M.D., M.B.A.  
9 
Mark W. Pagnano, M.D. 
10 
Daniel J. Berry, M.D.  
11 
 
12 
Principal Site:  Mayo Clinic, Rochester, Minnesota 
13 
 
14 
 
15 
 
16 
 
17 
 
18 
 
19 
 
20 
 
21 
 
22 
 
23 
 
24 
 
25 
 
26 
 
27 
 
28 
 
29 
 
30 
 
31 
 
32 
 
33 
 
34 
 
35 
 
36 
 
37 
 
38 
 
39 
 
40 
 
41 
 
42 
 
43 
 
44 
 
45 


 June 8, 2018 
 
Version 6 
 
2
INTRODUCTION 
46 
Stiffness after total knee arthroplasty (TKA) occurs when patients have difficulty flexing and 
47 
extending their knee for routine activities of daily living. Patients require 67 degrees of knee 
48 
flexion during the swing phase of gait, 83 degrees to ascend stairs, 90 degrees to descend stairs 
49 
and 93 degrees to rise from a standard chair.1 When less than 90 degrees of motion is reached 
50 
after TKA, the quality of life for patients is substantially decreased since simple activities like 
51 
walking can become difficult.2 3 
52 
 
53 
Despite advancements in surgical technique, implant design and pain management, arthrofibrosis 
54 
(i.e., malignant stiffness) remains one of the top five reasons for revision TKA. At the upcoming 
55 
2016 American Academy of Orthopaedic Surgeons annual meeting, Matthew P. Abdel, M.D., 
56 
and colleagues will present their data indicating a contemporary arthrofibrosis rate of 5.8 percent 
57 
after primary TKA at Mayo Clinic. In addition, 2.8 percent of patients require a manipulation 
58 
under anesthesia (MUA). While there are alternatives to MUA, physical therapy shows only 
59 
modest gains and surgery is reserved for patients that fail non-operative management. With 
60 
MUA, mean flexion improved 35 degrees.  However, 5 percent of patients failed to maintain at 
61 
least 90 degrees of flexion after the MUA at our institution. More concerning, these results were 
62 
similar to the previous decade, where the rate of arthrofibrosis was 5.4 percent, with 2.9 percent 
63 
requiring MUA. The only identifiable risk factor for MUA was previous knee operation.  Lastly, 
64 
a manipulation under anesthesia significantly increased the risk for revision.  As one can see, the 
65 
incidence of arthrofibrosis following primary TKA has remained unchanged over the past two 
66 
decades. With the exponential increase in primary TKAs, arthrofibrosis is a large burden to the 
67 
patient, surgeon and entire U.S. health care system ($8.75 billion annually). 
68 


 June 8, 2018 
 
Version 6 
 
3
  
69 
Preliminary clinical and translational research has indicated that an inflammatory disorder of the 
70 
musculoskeletal system may be responsible for post-operative stiffness in some patients.4-8 
71 
Although evidence remains limited to animal models, the inflammatory cascade plays a central 
72 
role in the formation, and recurrence, of arthrofibrosis, particularly at the time of insult (i.e. time 
73 
of index arthroplasty and/or MUA).7,9,10 This is essential as some insurance companies have 
74 
stopped covering this procedure. The purpose of this study was to determine the efficacy of 
75 
manipulation under anesthesia (MUA), with and without perioperative oral celecoxib and 
76 
intravenous (IV) corticosteroid. 
77 
 
78 
PATIENTS AND METHODS 
79 
Study Design 
80 
This study is a prospective, multicenter, randomized clinical trial (RCT) designed to evaluate the 
81 
use of anti-inflammatory medications for the management of arthrofibrosis following primary 
82 
TKA. Patients will be randomly assigned to either the control or experimental group. Both groups 
83 
will receive a manipulation under anesthesia (MUA) if flexion is < 90 degrees at 4 –12 weeks 
84 
postoperatively.  Manipulation under anesthesia is the international standard of care for early 
85 
arthrofibrosis.  The control group will not receive any IV corticosteroids or PO non-steroidal anti-
86 
inflammatory medications (NSAIDs).  The experimental group will receive a single dose of IV 
87 
corticosteroids (8 mg IV dexamethasone immediately prior to MUA) and 2 weeks of PO celecoxib 
88 
at a dose of 200 mg daily.  Many surgeons, including several at the Mayo Clinic, consider the use 
89 
of IV corticosteroids and PO celecoxib the standard of care with a MUA.   
90 
 
91 


 June 8, 2018 
 
Version 6 
 
4
Patients 
92 
Patients will be recruited from sixteen high-volume, academic, tertiary-care referral centers 
93 
(Table 1).  All enrolling centers have been vetted, as only surgeons that are members of the 
94 
prestigious closed Knee Society (representing the top 100 knee surgeons in the world) are 
95 
participating.  Patients approached for enrollment will have received a primary unilateral TKA 
96 
for a diagnosis of osteoarthritis. All primary TKA constructs will have constraint that is less than 
97 
that of varus-valgus constraint (VVC).  All VVC and hinged TKAs will be excluded.  Only 
98 
MUAs scheduled between 4 –12weeks postoperatively will be included.   
99 
 
100 
Institutional Review Board (IRB) approval will be obtained from all respective institutions prior 
101 
to initiation of the study.  The Mayo Clinic will serve as the coordinating site. Patients will be 
102 
excluded from the study if any of the following exist:  (1) intolerance to NSAIDs, (2) renal 
103 
dysfunction, (3) age < 18 or > 90 years,  (4) primary diagnosis of rheumatoid arthritis and (5) 
104 
patients with GFR <60 as the cut off for CKD (stage 3 CKD).  Use of non-steroidal anti-
105 
inflammatory medications during the first two weeks after manipulation under anesthesia will 
106 
exclude patients from participation in this study. However, celecoxib (a non-steroidal anti-
107 
inflamatory medication) will be provided for those patients randomized to the experimental 
108 
group, once daily for fourteen days following the manipulation under anesthesia. Aspirin, used 
109 
routinely for DVT prophylaxis post-operatively, did not restrict patients from participation in this 
110 
study. Patients who are on NSAIDs prior to MUA, is ok to enroll. Patient demographics were 
111 
noted, including age at index arthroplasty, sex, body mass index (BMI), ASA score, and 
112 
Charlson Index. 
113 
 
114 


 June 8, 2018 
 
Version 6 
 
5
Randomization 
115 
Patients will be randomized into one of 2 groups: (1) MUA only (i.e. control group) or (2) MUA 
116 
plus 8 mg of IV dexamethasone immediately before MUA, followed by 2 weeks of PO celecoxib 
117 
(200 mg daily) (experimental group). Assignment of patients into either group will be made prior 
118 
to the initiation of enrollment for the study. Patients will be randomized using a computer 
119 
generated (SAS PROC) block randomization schedule to ensure equivalent numbers of patients 
120 
in each group over the course of the study in case early stopping is required. The randomization 
121 
schedule will be generated by the Mayo Clinic Department of Epidemiology and Biostatistics 
122 
with the randomization list provided to the investigators prior to initiation of patient recruitment. 
123 
Neither the patient nor the treating physician were blinded the randomization group.   
124 
 
125 
Manipulation Under Anesthesia 
126 
Patients will undergo MUA per their institutional protocol.  As previously noted, these will be 
127 
completed between 4 and 10 weeks postoperatively for flexion < 90 degrees.  Patients will 
128 
receive sedation per their institutional protocol.  Physical therapy (either supervised or 
129 
unsupervised) will be prescribed 2 -3 times per week for 4 – 6 weeks thereafter.   
130 
 
131 
Outcome Measures 
132 
The primary outcome measure will be knee range of motion, including both passive and active 
133 
flexion and extension 6 weeks after the manipulation and 1 year from the date of the TKA. 
134 
Secondary outcomes will include comparison of Knee Society Scores (KSS), 12-item Short 
135 
Form Survey (SF-12v2), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 
136 
Promise-29 outcome form (Appendices 1-4). Outcomes will be documented pre-MUA, 6 weeks 
137 


 June 8, 2018 
 
Version 6 
 
6
after the MUA, and 1 year after the TKA. A standardize evaluation form will be shared amongst 
138 
all participating sites, and will be used consistently for all patients (Appendix 1-4). 
139 
 
140 
Power Analysis 
141 
The mean and standard deviation for sample size calculation were derived from a study by 
142 
Yercan et al. In that study, the authors found that the mean ROM following MUA was 114° ± 
143 
16°.11  We hypothesized that a 10° difference in total range of motion would constitute a 
144 
clinically significant difference. With a type I error rate of 5%, 108 total patients (54 per arm) are 
145 
required to have 90% power to detect this difference. Accounting for a dropout rate of 20%, 65 
146 
patients per arm (130 total patients) will be recruited. 
147 
 
148 
Statistical Analysis 
149 
All data will be summarized and reported descriptively using appropriate summary statistics, 
150 
including mean and standard deviation (SD) for continuous variables, and count and percentage 
151 
for categorical variables.  The analysis was focused on the two primary study outcomes: range of 
152 
motion (total arc of motion as well as angle of terminal knee flexion, measured in degrees), and 
153 
subjective outcome (KSS, SF-12v2, KOOS, and PROMIS).  Outcomes were compared between 
154 
the two study groups using two-sample t-tests if the data are approximately normally distributed; 
155 
if the data are not sufficiently normally distributed, non-parametric Wilcoxon rank sum tests was 
156 
used.  Since the subjects were assigned to the study groups in a randomized manner, no 
157 
significant differences between the subjects in the two groups were expected.  However, 
158 
apparent differences in subject demographics or baseline clinical data were evaluated, and 
159 
further analysis was undertaken using multivariable modeling to compare the two groups while 
160 


 June 8, 2018 
 
Version 6 
 
7
adjusting for other important variables.  When necessary and appropriate, the analysis was 
161 
adjusted for enrolling center.  Categorical outcomes were analyzed using chi-square tests and 
162 
logistic regression.  Separate analyses were performed for the 6-week and 1-year outcomes. All 
163 
statistical tests were two-sided and p-values less than 0.05 will be considered significant. 
164 
 
165 
Sources of Funding 
166 
This study is partially supported by the Knee Society Branded Multi-Center Randomized Clinical 
167 
Trial Grant. 
168 
 
169 
 
170 
 
171 
 
172 
 
173 
 
174 
 
175 
 
176 
 
177 
 
178 
 
179 
 
180 
 
181 
 
182 
 
183 
 
184 
 
185 
 
186 
 
187 
 
188 
 
189 
 
190 
 
191 
 
192 
 
193 
 
194 
 
195 
 
196 
 
197 
 
198 


 June 8, 2018 
 
Version 6 
 
8
 
199 
 
200 
 
201 
 
202 
 
203 
 
204 
 
205 
 
206 
 
207 
 
208 
 
209 
 
210 
TABLES 
211 
 
212 
Table 1. List of participating institutions included  
213 
Aria 3B Orthopaedic Specialists 
 
Colorado Joint Replacement  
 
Duke University Medical Center 
 
HipKnee Arkansas Foundation 
 
Hospital for Joint Diseases 
 
Hospital for Special Surgery 
 
Houston Methodist 
 
Joint Implant Surgeons 
 
Mayo Clinic 
 
New York-Presbyterian at Columbia University 
 
OrthoCarolina 
 
Rothman Institute 
 
Rush University Medical Center 
 
 
 
Cleveland Clinic 
 
University of Nebraska Medical Center 
 
University of Utah Orthopaedic Center 
 
 
214 
 
215 
 
216 
 
217 
 
218 
 
219 
 
220 
 
221 
 
222 
 
223 
 
224 
 
225 
 
226 


 June 8, 2018 
 
Version 6 
 
9
 
227 
 
228 
 
229 
 
230 
 
231 
 
232 
 
233 
 
234 
 
235 
 
236 
 
237 
 
238 
Table 2. Baseline demographics and clinical characteristics  
239 
Demographic and Clinical 
Characteristics 
MUA 
(N = X) 
MUA + AI 
(N = X) 
Demographic Characteristics 
     Age (year) 
     Sex (female/male) (no. of patients) 
     Weight (kg) 
     Height (cm) 
     BMI (kg/m2) 
     ASA Status (no. of patients) 
 
 
Implant Type 
 
 
Range of Motion 
     Total 
     Flexion Contracture 
     Extension Deficit 
 
 
 
240 
 
241 
 
242 
 
243 
 
244 
 
245 
 
246 
 
247 
 
248 
 
249 
 
250 
 
251 


 June 8, 2018 
 
Version 6 
 
10
 
252 
 
253 
 
254 
 
255 
 
256 
Table 3. Outcome following manipulation under anesthesia for stiffness after total knee 
257 
arthroplasty  
258 
Blood Loss, Drain Output, and Rate of 
Blood Transfusions 
MUA 
(N = X) 
MUA + AI 
(N = X) 
p value 
Six Week ROM 
     Total Pre-Manipulation 
     Flexion 
     Total 6 weeks Post-MUA 
     Flexion 
     < 90 degrees 
     < 80 degrees 
    Total 6 weeks Post-MUA 
     Flexion 
     < 90 degrees 
     < 80 degrees 
 
 
 
Six Week Subjective Outcome 
     KSS 
     SF-12v2 
     KOOS  
     Promis 29 
 
 
 


 June 8, 2018 
 
Version 6 
 
11
Blood Loss, Drain Output, and Rate of 
Blood Transfusions 
MUA 
(N = X) 
MUA + AI 
(N = X) 
p value 
One Year ROM 
     Total Pre-Manipulation 
     Flexion 
     Total 6 weeks Post-MUA 
     Flexion 
     < 90 degrees 
     < 80 degrees 
    Total 6 weeks Post-MUA 
     Flexion 
     < 90 degrees 
     < 80 degrees 
 
 
 
One Year Subjective Outcome 
     KSS 
     SF-12v2 
     KOOS  
     Promis 29 
 
 
 
 
259 
REFERENCES 
260 
 
261 
 
262 
1. 
Laubenthal KN, Smidt GL, Kettelkamp DB. A quantitative analysis of knee motion 
263 
during activities of daily living. Phys Ther. Jan 1972;52(1):34-43. 
264 
2. 
Williams DP, O'Brien S, Doran E, et al. Early postoperative predictors of satisfaction 
265 
following total knee arthroplasty. Knee. Dec 2013;20(6):442-446. 
266 
3. 
Fitzsimmons SE, Vazquez EA, Bronson MJ. How to treat the stiff total knee 
267 
arthroplasty?: a systematic review. Clin Orthop Relat Res. Apr 2010;468(4):1096-1106. 
268 
4. 
Abdel MP, Morrey ME, Barlow JD, et al. Myofibroblast cells are preferentially expressed 
269 
early in a rabbit model of joint contracture. J Orthop Res. May 2012;30(5):713-719. 
270 
5. 
Abdel MP, Morrey ME, Grill DE, et al. Effects of joint contracture on the contralateral 
271 
unoperated limb in a rabbit knee contracture model: a biomechanical and genetic study. J 
272 
Orthop Res. Oct 2012;30(10):1581-1585. 
273 
6. 
Barlow JD, Hartzler RU, Abdel MP, et al. Surgical capsular release reduces flexion 
274 
contracture in a rabbit model of arthrofibrosis. J Orthop Res. Oct 2013;31(10):1529-
275 
1532. 
276 
7. 
Barlow JD, Morrey ME, Hartzler RU, et al. Effectiveness of rosiglitazone in reducing 
277 
flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A 
278 
biomechanical, histological, and genetic analysis. Bone Joint Res. Jan 2016;5(1):11-17. 
279 


 June 8, 2018 
 
Version 6 
 
12
8. 
Nesterenko S, Morrey ME, Abdel MP, et al. New rabbit knee model of posttraumatic 
280 
joint contracture: indirect capsular damage induces a severe contracture. J Orthop Res. 
281 
Aug 2009;27(8):1028-1032. 
282 
9. 
Chevalier X, Goupille P, Beaulieu AD, et al. Intraarticular injection of anakinra in 
283 
osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled 
284 
study. Arthritis Rheum. Mar 15 2009;61(3):344-352. 
285 
10. 
Emami MJ, Jaberi FM, Azarpira N, Vosoughi AR, Tanideh N. Prevention of 
286 
arthrofibrosis by monoclonal antibody against vascular endothelial growth factor: a novel 
287 
use of bevacizumab in rabbits. Orthop Traumatol Surg Res. Nov 2012;98(7):759-764. 
288 
11. 
Yercan HS, Sugun TS, Bussiere C, Ait Si Selmi T, Davies A, Neyret P. Stiffness after 
289 
total knee arthroplasty: prevalence, management and outcomes. Knee. Mar 
290 
2006;13(2):111-117. 
291 
 
292 
 
293 

ICF_001.pdf: 
  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 1 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
 
 
RESEARCH PARTICIPANT CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
 
Study Title: Manipulation Under Anesthesia (MUA) to Treat Postoperative Stiffness after 
Total Knee Arthroplasty: A Multicenter Randomized Clinical Trial 
 
IRB#: 15-009075 
 
Principal Investigator: Dr. Matthew Abdel and Colleagues 
 
Please read this information carefully. It tells you important things about this research study. A 
member of our research team will talk to you about taking part in this research study.  If you 
have questions at any time, please ask us. 
 
Take your time to decide.  Feel free to discuss the study with your family, friends, and healthcare 
provider before you make your decision.   
 
To help you decide if you want to take part in this study, you should know: 
• Taking part in this study is completely voluntary.  
• You can choose not to participate.  
• You are free to change your mind at any time if you choose to participate.   
• Your decision won’t cause any penalties or loss of benefits to which you’re otherwise 
entitled. 
• Your decision won’t change the access to medical care you get at Mayo Clinic now or in 
the future if you choose not to participate or discontinue your participation.   
 
For purposes of this form, Mayo Clinic refers to Mayo Clinic in Arizona, Florida and Rochester, 
Minnesota; Mayo Clinic Health System; and all owned and affiliated clinics, hospitals, and 
entities. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
want to take part. We will give you a copy of this form to keep. A copy of this form will be put 
in your medical record. 
 
 
 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 2 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
 
CONTACT INFORMATION 
 
 
You can contact … 
At … 
If you have questions about … 
Principal Investigator: 
Dr. Matthew Abdel 
 
Study Team Contact: 
Orthopedic Study 
Coordinator Staff 
 
 
Phone: 
(507) 284-2511 
 
Phone: 
(507) 538-3562 
 
Address: 
Mayo Clinic 
200 First Street SW 
Rochester, MN 55905 
 Study tests and procedures 
 Research-related injuries or 
emergencies 
 Any research-related concerns or 
complaints 
 Withdrawing from the research study 
 Materials you receive 
 Research-related appointments 
Mayo Clinic 
Institutional Review 
Board (IRB) 
Phone: 
(507) 266-4000 
Toll-Free: 
(866) 273-4681 
 Rights of a research participant 
 
Research Subject 
Advocate 
(The RSA is independent 
of the Study Team) 
Phone: 
(507) 266-9372 
 
Toll-Free: 
(866) 273-4681 
 
E-mail: 
researchsubjectadvocate@mayo.edu 
 
 Rights of a research participant 
 Any research-related concerns or 
complaints 
 Use of your Protected Health 
Information 
 Stopping your authorization to use 
your Protected Health Information 
Patient Account Services 
 
Toll-Free:  
(844) 217-9591 
 Billing or insurance related to this 
research study 
 
Other Information:   
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Website will not include information that can identify you. At most, the 
Website will include a summary of the results. You can search this Website at any time. 
 
 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 3 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
 
1. 
Why are you being asked to take part in this research study? 
 
 
You have exhibited a rare complication called postoperative stiffness that affects less than 5% of 
patients following a knee replacement surgery. While this complication is known, the cause and 
optimal treatment for this condition remains unknown.  
 
 
2. 
Why is this research study being done? 
 
 
Postoperative stiffness has been poorly studied. The best treatment option for this condition at 
this time is manipulation under anesthesia (MUA). While many patients regain range of motion 
not all return to optimal outcome.  
 
It is thought that inflammation can contribute to postoperative stiffness. We would like to 
investigate if anti-inflammatory medications can limit scar formation, and improve knee function 
following MUA. 
 
 
3. 
Information you should know 
 
 
Who is Funding the Study? 
 
A Knee Society grant is funding a portion of this multi-center study. 
 
 
4. 
How long will you be in this research study? 
 
 
Your participation in this study will be for about 1 year following your MUA.   
 
 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 4 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
 
5. 
What will happen to you while you are in this research study? 
 
 
If you agree to be in the study, you will be randomly assigned (like a coin toss) to receive MUA 
alone or MUA with anti-inflammatory medications, celecoxib and dexamethasone. You and the 
Principal Investigator can’t choose your study group. You will have an equal chance of being 
assigned to either group.  
 
If you are assigned to the MUA with anti-inflammatory medication group, an intravenous (into 
your vein) dose of dexamethasone will be given to you at the time of MUA. If in this group, you 
will also receive celecoxib. Similar to Advil (ibuprofen), this medication is a Non-steroidal Anti-
inflammatory drug (NSAID) and decreases inflammation. It has fewer gastrointestinal side 
effects than typical NSAID’s. You will be given a prescription to take to the pharmacy of your 
choice. You will be asked to take the medicine one time daily either at morning or night time 
with food and water for 2 weeks following MUA.  
 
Whether you receive the anti-inflammatory medications or not, you will be followed throughout 
your routine follow up to assess your continued progress. 
 
You will fill out questionnaires about your knee and quality of life. You will do this at the time 
you consent and at your 6-week and 1-year follow up visits. We hope that you will answer all of 
the questions, but you can skip any questions you don’t want to answer. The questionnaires will 
take about 15-20 minutes to complete. 
 
 
6. 
What are the possible risks or discomforts from being in this research 
study? 
 
 
Risks associated with you participation in this study remain small.  
 
Both celecoxib and dexamethasone are FDA approved to treat conditions of inflammation. Many 
people using either of these medications do not have serious side effects. 
 
Side effects of an intravenous dexamethasone may include: nausea, vomiting, heartburn, 
headache, dizziness, trouble sleeping, appetite changes, increased sweating, acne, or 
pain/redness/swelling at the injection site. Additionally, this medication may make your blood 
sugar level rise, which can cause or worsen diabetes.  
 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 5 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
Celecoxib has potential side effects as well including: stomach upset or gas and rise in blood 
pressure. Some people have an allergy to NSAID’s, which could cause severe headache, 
unexplained weight gain, and swelling of the hands or feet. Rarely, NSAID medications can 
impair the function of your kidneys and liver. However, the dose and duration of treatment used 
in this study would make either of these side effects exceedingly rare.  
 
 
7. 
Are there reasons you might leave this research study early? 
 
 
You may decide to stop at any time. You should tell the Principal Investigator if you decide to 
stop, and you will be advised whether any additional tests may need to be done for your safety. If 
you leave this research study early, or are withdrawn from the study, no more information about 
you will be collected; however, information already collected about you in the study may 
continue to be used. 
 
 
8. 
What if you are injured from your participation in this research study? 
 
 
Where to get help: 
If you think you have suffered a research-related injury, you should promptly notify the Principal 
Investigator listed in the Contact Information at the beginning of this form. Mayo Clinic will 
offer care for research-related injuries, including first aid, emergency treatment and follow-up 
care as needed. 
 
Who will pay for the treatment of research related injuries: 
Care for such research-related injuries will be billed in the ordinary manner, to you or your 
insurance.  You will be responsible for all treatment costs not covered by your insurance, 
including deductibles, co-payments and coinsurance. 
 
 
9. 
What are the possible benefits from being in this research study? 
 
 
The proposed benefits of this study would be to improve the treatment options for future patients 
experiencing your condition. While your knee may or may not benefit from this study, future 
patients may gain from the data collected in this study.  


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 6 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
It is our hope that manipulation along with the use of anti-inflammatory medications will 
improve knee range of motion and knee function for patients experiencing postoperative 
stiffness. 
 
 
10. 
What alternative do you have if you choose not to participate in this 
research study? 
 
 
You do not have to be in this study to receive treatment for your condition. Your other choices 
may include: 
• MUA without anti-inflammatory medications 
• No MUA, but continued physical therapy 
 
Talk to your Principal Investigator or your doctor if you have any questions about any of these 
treatments or procedures. 
 
 
11. 
What tests or procedures will you need to pay for if you take part in this 
research study?  
 
 
You and/or your insurance will need to pay for all tests and procedures for this study as they are 
considered part of your clinical care.  
 
If you have billing or insurance questions call Patient Account Services at the telephone 
number provided in the Contact Information section of this form. 
 
 
12. 
Will you be paid for taking part in this research study? 
 
 
You will not be paid to take part in this research study. 
 
 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 7 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
 
 
13. 
How will your privacy and the confidentiality of your records be protected? 
 
 
Mayo Clinic is committed to protecting the confidentiality of information obtained about you in 
connection with this research study. Data will be stored in electronic files and/or a cabinet, with 
access to study personnel as authorized by the investigator. The investigator will review the data 
on a regular basis (at least annually) to verify the validity of the data. 
 
During this research, information about your health will be collected. Under Federal law called 
the Privacy Rule, health information is private. However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so. Information about you and your health cannot be used in this 
research study without your written permission. If you sign this form, it will provide that 
permission.   
 
Health information may be collected about you from: 
• Past, present and future medical records. 
• Research procedures, including research office visits, tests, interviews and 
questionnaires. 
 
Why will this information be used and/or given to others? 
• To do the research. 
• To report the results. 
• To see if the research was done correctly. 
 
If the results of this study are made public, information that identifies you will not be used. 
 
Who may use or share your health information? 
• Mayo Clinic research staff involved in this study.  
 
With whom may your health information be shared?  
• The Mayo Clinic Institutional Review Board that oversees the research.  
• Other Mayo Clinic physicians involved in your clinical care.  
• Researchers involved in this study at other institutions. 
• Federal and State agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health and other United States 
agencies) or government agencies in other countries that oversee or review research. 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 8 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
• The sponsor(s) of this study and the people or groups it hires to help perform this 
research. 
• A group that oversees the data (study information) and safety of this research. 
 
In addition, individuals involved in study oversight and not employed by Mayo Clinic may be 
allowed to review your health information included in past, present, and future medical and/or 
research records. This review may be done on-site at Mayo Clinic or remotely (from an off-site 
location). These records contain information that directly identifies you. However, the 
individuals will not be allowed to record, print, or copy (using paper, digital, photographic or 
other methods), or remove your identifying information from Mayo Clinic. 
 
Is your health information protected after it has been shared with others? 
Mayo Clinic asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside Mayo Clinic, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
Your Privacy Rights 
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
If you cancel your permission to use or share your health information, your participation in this 
study will end and no more information about you will be collected; however, information 
already collected about you in the study may continue to be used. If you choose not to take part 
or if you withdraw from this study, it will not harm your relationship with your own doctors or 
with Mayo Clinic. You can cancel your permission to use or share your health information at any 
time by sending a letter to the address below: 
 
Mayo Clinic 
Office for Human Research Protection 
ATTN:  Notice of Revocation of Authorization 
200 1st Street SW 
Rochester, MN  55905 
 
Alternatively, you may cancel your permission by emailing the Mayo Clinic Research Subject 
Advocate at: researchsubjectadvocate@mayo.edu 
 
Please be sure to include in your letter or email: 
• The name of the Principal Investigator, 
• The study IRB number and /or study name, and 
• Your contact information. 
 


  
 
 
 
 
 
 
 
 
 
 
 
Approval Date:  
February 4, 2022 
Not to be used after: February 3, 2023  
 
IRB#: 15-009075 00              E-sign 
Page 9 of 9 
IRB Doc. Ctrl # 10013.26 
 
 
 
 
 
 
 
Name and Clinic Number 
Your permission lasts until the end of this study, unless you cancel it.  Because research is an 
ongoing process, we cannot give you an exact date when the study will end. 
 
 
ENROLLMENT AND PERMISSION SIGNATURES: 
 
 
Your signature documents your permission to take part in this research.  
 
 
 
  
 
 
 
          
 
 
    
        
Printed Name  
 
 
 
Date (mm/dd/yyyy) 
 
Time (hh:mm am/pm) 
 
 
 
_______________________________ 
Signature 
 
Person Obtaining Consent  
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
  
 
 
 
        
 
 
 
    
         
Printed Name  
 
 
 
Date (mm/dd/yyyy) 
 
Time (hh:mm am/pm) 
 
 
_______________________________ 
Signature 
 
 
sigParticipant
sigPOC
chkEsi
dteParticipantSig
dtePOCSig
prtParticipantName
prtPOCName
sigWitness