The Effect of Mindfulness-Based Stress Reduction on Pain and Function in Persons With Knee Osteoarthritis
Phase: NA
Conditions: Knee Osteoarthritis
Sponsor: University of California, Davis

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 1 of 13 
 
Revised: February 20, 2018 
1) Protocol Title 
The Effect of Mindfulness-Based Stress Reduction on Pain and Function in Persons 
with Knee Osteoarthritis 
 
Protocol Version Date: April 3, 2018  
 
2) Study Aims 
Our goals are to establish feasibility of a controlled trial at UC Davis comparing the 
effects of Mindfulness-Based Stress Reduction (MBSR) versus online MBSR versus 
an active comparison Health Enhancement Program (HEP) (Aim 1) on measures of 
pain and function in persons with knee osteoarthritis (OA) (Aim 2), and to collect 
preliminary data on the effect of MBSR on serum stress and inflammatory markers 
(Aim 3). This pilot study will be complete in one year. 
 
Specific Aim 1: To determine the feasibility of enrolling symptomatic knee OA 
patients and performing a non-randomized study comparing MBSR vs online MBSR 
vs HEP. 
 
Hypotheses 1: It will be possible in the UC Davis Medical System to enroll knee OA 
patients and perform an RCT. 
 
Specific Aim 2: Compare the effect of MBSR vs online MBSR vs HEP on pain and 
function limitations in knee OA. 
 
Hypothesis 2: Compared with HEP, MBSR will result in significantly greater 
improvement in pain intensity and function.  
 
Specific Aim 3: Investigate whether MBSR and online MBSR result in decreases in 
serum cortisol level or changes in eicosanoid parameters compared with HEP 
intervention. 
 
Hypothesis 4: MBSR will result in decreases in serum cortisol level and changes in 
eicosanoid parameters compared with HEP intervention. 
 
3) Background 
Rationale: Current treatments for OA and pain in OA all are non-ideal. Non-steroidal 
anti-inflammatory drugs (NSAIDs) are associated with a high risk of gastrointestinal 
bleeding and cardiovascular events1,2 and are only moderately effective for treating 
pain, while opiates and surgery carry other risks. There is evidence that interventions 
affecting emotional state may moderate pain in OA, both in our work and elsewhere3-
5. MBSR6 is a secular program that trains mindfulness meditation for stress reduction 
and to increase emotional regulation skills. Meta-analyses of mindfulness-based 
interventions (MBIs) have demonstrated reliable clinical efficacy, specifically in the 
reduction of symptoms of stress, depression and anxiety7. A recent meta-analysis of 
MBIs for non-OA chronic pain patients determined that mindfulness meditation is 
associated with decreases in pain, as well as improvement in depression and quality 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 2 of 13 
 
Revised: February 20, 2018 
of life compared with all types of control conditions8. To our knowledge, there are no 
prior peer-reviewed studies that answer whether an MBSR intervention improves pain 
or function in knee OA.  
 
Research is needed to investigate the relation of mindfulness practices with 
stress hormones and markers of inflammation. Prior studies investigating the 
effect of mindfulness interventions on changes in the level of the stress hormone 
cortisol conflict, with some studies showing no effect and others demonstrating 
significant changes with mindfulness training 9,10; one study of a short-term MBI 
demonstrated reductions over 10 days of the intervention in levels of inflammatory 
cytokines interleukin-6 and TNF-alpha 11. 
   
 
Preliminary data - MBSR effect on pain and cognitive reappraisal in adults with 
primary anxiety disorders: In a sample of 39 adults with primary anxiety disorders, 
we found that standard MBSR produced significant decreases in Patient Reported 
Outcomes Measurement Information System (PROMIS) measures of pain intensity 
(p<.001) and interference (p<.001). This confirms that MBSR reduces pain 
experience in anxiety disorder patients with a variety of secondary pain problems.  
 
Description of intervention and comparator: The intervention will be MBSR as 
described above. The online MBSR course will be offered through: 
http://www.breathworks-mindfulness.org.uk/mindfulness-for-health. We propose to 
use an active control training, the Health Enhancement Program (HEP), an 
intervention designed to isolate mindfulness as a testable active ingredient12. HEP and 
MBSR are structurally equivalent, both using a group format that meets once a week 
for 2.5  hours for 8 weeks with an “all day” component  after week 6, plus home 
participation. The content of the HEP intervention meet the following criteria: (1) 
class activities match MBSR activities as closely as possible, (2) activities represent 
valid, active, therapeutic ingredients in their own right, and (3) these ingredients do 
not include mindfulness. We will also measure steroid and oxylipin inflammation 
markers through the UC Davis designated metabolomics core at baseline and end of 
intervention. 
 
Description of outcome measures: Participants will be asked at each time point to 
complete a validated, widely-used disease- and joint-specific questionnaire-based 
knee OA symptom evaluation, the Western Ontario and McMaster University 
Osteoarthritis Index (WOMAC)13. We will ask participants to record baseline and 
weekly WOMAC pain and function, the number of minutes of meditation practice 
and frequency of use of cognitive reappraisal. To evaluate changes in psychological 
functioning, we will administer a brief batter of self-report questionnaires that 
measure state emotion, emotion regulation, mindfulness skills, compassion, and pain 
catastrophizing before the intervention, midway and after the final week. For oxylipin 
and steroid profiling, usually 84 markers are positively detected and quantified even 
in healthy subjects using 150 ul plasma or serum. We expect higher concentrations of 
these markers in elderly subjects with OA pain. We expect differences in 
concentrations of these markers for MBSR or HEP groups. 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 3 of 13 
 
Revised: February 20, 2018 
Methodology, selection criteria and recruitment: We will recruit 30 adults 50-80 
years of age with symptomatic knee OA defined as pain in the index joint on most 
days of the past month, and radiographically confirmed OA structural lesions 
(Kellgren/Lawrence grade ≥ 2); we expect to have 20% dropout, leaving 24 
participants completing the study. We will exclude participants using antipsychotic 
medications, who have alcohol or drug dependency, are scheduled to have joint 
replacement surgery in either leg within the next six months, or have inflammatory 
arthritis or avascular necrosis. The Clinical Trials arm of our Center for 
Musculoskeletal Health has successfully participated in and recruited numerous knee 
OA-related trials over a decade, and we are confident we will be able to achieve our 
goal. 
 
Data Analysis Approach: Given that the proposed study is a feasibility study with 
very small numbers of participants, we will likely not reach significance for the pain 
outcomes; however, intention to treat (ITT) analysis will be undertaken to evaluate 
the effect of MBSR vs. HEP or vs. online MBSR. First we will compare the baseline 
characteristics using χ2 test for categorical or nominal variables and t-test for 
continuous variables between MBSR and HEP groups. Second, we will assess 
whether, compared to HEP, MBSR results in significantly greater improvement in 
WOMAC pain or daily function, as well as for steroid and inflammatory markers. 
Using mixed models, we will compare the effect of MBSR vs. HEP on changes in 
WOMAC pain at each weekly visit from baseline using a mixed-effects regression 
model. Oxylipin and steroid profiles will be assessed by FDR-corrected univariate 
statistics in addition to partial least square regression analyses for differences in 
metabolites that are associated with pain change, in addition to correlation analysis of 
metabolic changes along the different time points of blood withdrawals. 
 
4) Inclusion and Exclusion Criteria 
We will be enrolling 30 subjects who have symptomatic knee osteoarthritis. 
 
a) Inclusion Criteria 
 Male or female, aged 50-80 years 
 Positive “Frequent Knee Pain” question 
 Radiographically confirmed knee OA (Kellgren/Lawrence ≥ 2) 
 
b) Exclusion criteria 
 Scheduled to have knee replacement surgery within 6 months from enrollment 
 Rheumatoid arthritis or another inflammatory arthritis 
 Known avascular necrosis 
 Failure to comply with run-in procedures: poor attendance or non-compliant 
with completing the activity 
 Major psychiatric illness, cognitive impairment or alcohol/substance abuse 
 Non-English speaking 
 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 4 of 13 
 
Revised: February 20, 2018 
Participants will be recruited by referral from their physician and posted 
announcements in the Department of Orthopedics Clinics, UC Davis Orthopaedic 
Surgery clinics, UC Davis Rheumatology Clinics, UC Davis primary care clinics, and 
local Sacramento and Davis senior community. 
 
We will exclude the following special populations: adults unable to consent, 
individuals who are not yet adults, pregnant women, prisoners, and any UC Davis 
staff directly under the oversight of the Principle Investigators. 
 
5) Study Timelines 
The duration of an individual subject’s participation in the study will be at least 10 
weeks starting from the screening visit all the way to the follow-up visit. 
 
The in-person MBSR course consists of 8 weekly classes plus 1 all-day class between 
Weeks 6 and 7, and is sequential. Depending on when a participant is consented, they 
may have to wait until a new 8-week course is available in order to begin. The HEP 
course also consists of 8 weekly classes and will start when a group of 7-10 
participants have been assigned to the HEP intervention. The online MBSR course is 
designed to last 8 weeks and can be started at any time. 
 
Since initiation of the in-person MBSR or HEP courses will depend upon when 
subjects are enrolled, it is not possible to provide the maximum length of time for a 
subject’s participation. However long the subject’s participation, they are only 
expected to complete 2 in-clinic visits and 8 weeks of class (plus 1 all-day class for 
MBSR). 
 
Visits to the clinic may last from 1 to 2 hours. Weekly classes are 2.5 hours with the 
one-day retreat lasting from 10am to 5pm on a weekend day. The online MBSR 
course is roughly 20 minutes per day for 6-7 days of the week for 8 weeks. 
 
We expect enrollment to occur over the course of 6 months. Final data collection is 
anticipated at 15 months. 
 
6) Study Endpoints 
Anticipated results, interpretation and pitfalls: We anticipate success in the 
feasibility Aim, and also that, compared with HEP, MBSR will result in greater 
improvement in pain and function in persons with knee OA. If this test study finds a 
positive feasibility result, we intend to proceed with a formal NIH clinical trial to 
establish the basis for introduction of MBSR practice into the standard 
armamentarium of knee OA treatment, as a primary or adjunct treatment. A negative 
result would also be important. If we have problems recruiting or bringing 
participants through the intervention, it will allow us to refine our approaches. 
Finally, a completely negative result with regard to pain and function here would 
have a critically important impact as well. MBSR is gaining significant attention in 
medicine as a potentially valuable clinical and research tool for pain and other 
conditions. If we find no association with important clinical outcomes in the fastest 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 5 of 13 
 
Revised: February 20, 2018 
growing major painful health condition (OA), it would necessarily begin a critical 
discussion regarding the value of MBSR in the treatment of knee OA, as well as in 
other pain conditions.  
 
7) Procedures Involved 
The study will consist of two in-person clinic visits and the 8-week MBSR or HEP 
course. 
 
Visit 1: Screening/Baseline (Clinic) 
The following procedures will be performed: 
1. Informed consent 
2. Demographics (including age, sex, race, religious affiliation) 
3. Tobacco smoking status 
4. Vital signs (heart rate) 
5. Height, weight, BMI 
6. Medical/surgical history including history of pregnancies if applicable 
7. Concomitant medication review 
8. Inclusion/exclusion review 
9. Blood draw (about 1.5 ml for oxylipin, cortisol, and other metabolite analyses 
with any leftover specimens banked for future use, 3 ml for CRP and 3 ml for 
ESR) 
10. Saliva collection (about 1ml for cortisol analysis with the any leftover specimens 
banked for future use) 
11. Surveys: Western Ontario and McMaster Universities Osteoarthritis Index 
(WOMAC), Emotion Regulation Questionnaire (ERQ), Five Facet Mindfulness 
Questionnaire (FFMQ), Pain Catastrophizing Scale (PCS) 
 
Weeks 1 through 8 (MBSR or HEP course) 
After the participant is verified as eligible to be enrolled and as completed all pre-
treatment (i.e., baseline) assessments, they will be assigned to either the in-person 
MBSR course, the online MBSR course or the in-person group HEP course. 
 
MBSR & HEP Courses 
The weekly in-person HEP courses will be held at UC Davis Medical Center in 
Sacramento. The in-person MBSR courses have three locations: UCDMC, Sutter 
Health University in Sacramento, and Davis Holistic Health Center in Davis. Weekly 
classes will consist of didactic content, guided experiential meditation exercises, and 
group discussion. Additionally, the MBSR course will have an all-day class on a 
weekend day to be completed between Weeks 6 and 7. 
 
The online MBSR course can be accessed at home or any place of the subject’s 
choosing and will also consist of training in mindfulness meditation and mindfulness 
exercises. Training takes place twice per day, 10 minutes per session. 
 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 6 of 13 
 
Revised: February 20, 2018 
Participants will complete self-reported online surveys (WOMAC) , weekly during 
treatment and at 2-week follow-up. ERQ will be completed once during the midpoint 
(around Week 5). 
 
Visit 2: 2-Week Follow-Up (Clinic) 
Within 2 weeks of the final class, subjects will return to clinic to complete the 
following: 
1. Vitals (heart rate) 
2. Blood draw (same as Visit 1) 
3. Saliva collection (same as Visit 1) 
4. Surveys  (same as Visit 1) 
 
All courses will be provided to enrolled subjects free of charge. 
 
Schedule of Events 
 
Visit 1: 
Screening/
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Week 
5 
Week 
6 
Week 
7 
Week 
8 
Visit 2: 2-Week 
Follow-Up 
Informed Consent 
X 
 
 
 
Inc/Exc Review 
X 
 
 
 
Vitals X 
 
 
 
X
Medical/Surgical 
History 
X 
 
 
 
 
 
 
 
 
 
Concomitant 
Medication 
X 
 
 
 
 
 
 
 
 
 
Demographics X 
 
 
 
Blood Draw 
X 
 
 
 
X
Saliva Collection 
X 
 
 
 
X
WOMAC X 
X 
X
X
X
X
X
X X 
X
ERQ X 
 
X
 
 
X
FFMQ X 
 
 
 
X
PCS 
X 
        
X 
Courses Below Will Be Assigned by Study Investigator
In-Person MBSR 
Class 
 
X X X X X 
Xa X 
X 
 
Online MBSR Class 
 
Xb 
Xb
Xb
Xb
Xb
Xb
Xb 
Xb 
In-Person HEP 
Class 
 
X X X X X X X X 
 
aSubjects assigned to the in-person MBSR course will also complete an all-day class on a weekend day between Weeks 6 and 7 
bSubjects assigned to the online MBSR course will complete self-directed classes at home 
 
8) Data and/or Specimen Management and Confidentiality 
We will implement a mixed model to examine the effect of treatment (MBSR vs 
online MBSR vs HEP) on changes in pain and psychological functioning from pre, 
weekly during treatment, post-treatment to 2-week follow-up. Because this is a pilot 
study with only 30 patients, there is no need for a power analysis. Each participant 
will be given a unique identification number that will be linked to all data collected. 
Names will not be used. This will provide confidential responses. Self-report data will 
be stored in password protected and encrypted spreadsheets. Blood samples will be 
stored in sub-zero freezers at the Center for Musculoskeletal Disorders at UC Davis 
medical Center in locked research labs and linked only to identification numbers (no 
names). All data will be stored for at least 7 years. All research personnel will 
complete HIPAA and confidentiality training.  

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 7 of 13 
 
Revised: February 20, 2018 
 
9) Data and/or Specimen Banking 
Left over blood or saliva samples will be banked for future use. At the end of the 
study, the key that links the samples to the subjects will be destroyed. All samples 
will be stored without identifiers. As this is a pilot study, we may develop novel ideas 
in the future as it relates to this study and may want to conduct additional analyses. 
The samples will be stored indefinitely in a controlled-accessed location. We do not 
intend to share these samples outside of the research group. 
 
10) 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
There will be continuous safety surveillance with emphasis on the potential side 
effects of each intervention, as detailed below. Participation in the study will be 
discontinued if the subject fails to adhere to the study requirements in a way that 
may cause harm to him or herself or seriously interfere with the validity of the 
study results; or the investigator determines that further participation would be 
detrimental to the subject’s health or well-being. Subjects who are injured as a 
result of being in this study will have treatment available. The costs of such 
treatments may be covered by the University of California depending on a number 
of factors.  
 
Data and Safety Monitoring Plan (DSMP): The Data and Safety Monitoring 
Plan for the proposed project incorporates the policies on human subject data and 
safety monitoring specified by the UC Davis IRB. Since this is not a NIH-defined 
Phase III Clinical Trial and it is a low risk trial at a single site, a formal Internal 
and External Review Board is not required, and the PI can conduct the data and 
safety monitoring in conjunction with the UC Davis IRB. The PI of the project 
along with relevant project staff will meet regularly with the Clinical 
Coordinator/Data Manager (post-doctoral fellow) to review issues of data quality 
or other issues that might arise. The PI will be responsible for evaluating any 
adverse event and if necessary reporting it to the IRB. 
 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 8 of 13 
 
Revised: February 20, 2018 
1. Risk assessment – minimal risk: This study represents a minimal risk to 
study participants since it is a behavioral intervention study and prior studies 
with mindfulness meditation (MBSR) have not demonstrated the occurrence 
of serious adverse events. 
 
2. Description of adverse event grading and anticipated adverse events: An 
adverse event (AE) is here defined as any unfavorable and unintended sign, 
symptom, injury or disease temporarily associated with an intervention or 
procedure, regardless of whether it is considered related to an intervention or 
procedure that occurs during the course of the study. There is a minimal risk 
of an unfavorable psychological event, which has generally not been observed 
in other trials of MBSR. Therefore, the likelihood and seriousness of this risk 
is small. 
 
3. Description of monitoring study progress and safety of human subject 
participants: The principal investigator, Barton L. Wise, MD, MSc, FACP, 
has primary responsibility for the overall conduct of the study and for the 
safety of participating human subjects. The PI will ensure that (1) the 
informed consent process is conducted appropriately and that informed 
consent is obtained prior to proceeding with any study procedures; (2) only 
eligible subjects, per protocol eligibility criteria, are enrolled in the study; (3) 
data are collected and analyzed per protocol requirements; (4) procedures are 
implemented to ensure that the project is consistently monitored for possible 
adverse events; (5) adverse events are reviewed promptly and reported as 
required to the IRB; (6) the privacy and confidentiality of study subjects is 
maintained. Monitoring for adverse events will occur in real time at the single 
site, and the PI will be made aware of potential adverse events immediately 
during the conduct of the trial by study staff. When an event occurs, the PI 
will make an estimation of whether it is serious or likely to be related to the 
study interventions; serious adverse events or reportable new information will 
be reported to the IRB following local guidelines If events are minor or 
unrelated, they will be collected and reviewed on a yearly basis to examine for 
unforeseen patterns. While implementation of aspects of the DSMP may be 
delegated to members of the research team, the PI maintains ultimate 
responsibility for the project and for the safety of study participants. The PI, 
Dr. Wise, has served in the past as designated safety officer for multiple 
NIH/NIAMS sponsored clinical trials, and thus has significant experience 
with the process and with consideration of potential adverse events. 
 
11) 
Withdrawal of Subjects 
The study doctor or the IRB can remove subject from the research study without 
their approval. The study doctor may stop subjects’ participation in the study at 
any time for any reason if, in his/her judgment, continuation of study is not in the 
subject’s best interest. Possible reasons for stopping study participation may 
include: 
 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 9 of 13 
 
Revised: February 20, 2018 
 Subject does not meet study requirements 
 Subject does not follow the study instructions given by the study doctor or 
study staff; 
 Subject does not show up for scheduled visits; 
 The study doctor determines that it is not in the best interest of the subject to 
continue in the study; 
 Administrative reasons 
 
12) 
Risks to Subjects 
Possible risks/inconveniences to subjects include: 
1. Venipuncture: Pain, bruising, or infection at the site of blood draw. 
2. Loss of confidentiality: Participation in research can involve loss of privacy. 
Research records will be kept confidential to the extent permitted by law. 
Subjects will be identified by a code, and personal information from records 
will not be released without written permission. Subjects will not be 
personally identified in any publication about the study. 
3. Mindfulness-Based Stress Reduction Training (MBSR): There is minimal risk 
associated with participating in the MBSR intervention. If we or our 
contracted trainer observes any evidence of significant depression we will 
refer the participant to psychological services. 
4. Health Enhancement Program (HEP): There is minimal risk associated with 
participation in the HEP alternate intervention. The only potential risks are the 
same as attending a series of sit down lectures. If we observe any unusual or 
unforeseen behavior, we will refer the participant to psychological services. 
 
13) 
Potential Benefits to Subjects 
There is no guaranteed benefit to subjects who participate in this study. The 
benefits of participation in this study include social participation in a group 
activity and the opportunity to contribute to scientific understanding that may lead 
to treatment for an unmet health need. The information gathered in this study will 
be very important in learning whether targeted MBSR can improve pain or 
function in osteoarthritis. Improvement in pain or function could promote health 
and improved social participation in older adults. 
 
14) 
Multi-Site Research 
N/A 
 
15) 
Community-Based Participatory Research 
N/A 
 
16) 
Sharing of Results with Subjects 
 
Research results for each individual participant will not be shared.   
 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 10 of 13 
 
Revised: February 20, 2018 
17) 
Prior Approvals  
N/A 
 
18) 
Provisions to Protect the Privacy Interests of Subjects 
Subject’s personal and medical information will be kept confidential. Each 
subject will be given a subject identification number that will be used throughout 
the study on any source documents, blood samples or other study materials.  
In addition to signing a consent form subjects will also be signing a HIPAA 
release form, which allows the study team to access subject UCD medical records 
for research purposes only. On the HIPAA form subjects can select what parts of 
their medical history they are giving us permission to access. 
 
During the consent process subjects will be provided with an explanation 
regarding how we plan on protecting their privacy by keeping their personal and 
medical records confidential.  
 
Only trained study staff will have access to study records, which will be stored in 
a locked cabinet in a secure building. 
 
19) 
Compensation for Research-Related Injury 
Subjects will be provided with contact information and asked to promptly report 
any injury believed to be related to their participation in this study. If a subject is 
injured as a result of being in this study, the University of California will provide 
necessary medical treatment. Depending on the circumstances, the costs of the 
treatment may be covered by the University or may be billed to the subject’s 
insurance company just like other medical costs. The University does not 
normally provide any other form of compensation for injury. 
 
20) 
Economic Burden to Subjects 
The investigator is paying for all study procedures and subjects will receive 
compensation for participating in the study; therefore there will not be any costs 
that the subjects will be responsible for related to their participation in this study. 
 
21) 
Drugs or Devices 
Not applicable. 
 
22) 
ClinicalTrials.gov Registration  
This study will be registered with ClinicalTrials.gov. 
 
Section 1:  NIH Funded Studies 
If yes to BOTH, the study must be registered on Clinicaltrials.gov. 
Yes  
 
This study is funded by the NIH. (If this study is not funded by NIH, go to Section 
2.) 
 
One or more human subjects will be prospectively assigned to one or more 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 11 of 13 
 
Revised: February 20, 2018 
interventions (which may include placebo or other control) to evaluate the effects of 
those interventions on health-related biomedical or behavioral outcomes. 
 
Section 2:  Studies subject to FDA jurisdiction 
If yes to ANY the study must be registered on Clinicaltrials.gov. 
Yes 
 
 
This is a prospective clinical study of health outcomes in human subjects that 
compares an intervention with an FDA-regulated device against a control. This is 
not a small clinical trial to determine the feasibility of a device, or a clinical trial to 
test prototype devices where the primary outcome measure relates to feasibility 
and not to health outcomes. 
 
This is a pediatric postmarket surveillance of a device as required under section 
522 of the Federal Food, Drug, and Cosmetic Act. 
 
This is a controlled clinical investigation, other than a phase I clinical 
investigation, of a drug subject to section 505 of the Federal Food, Drug, and 
Cosmetic Act or to section 351 of the Public Health Service Act. 
To view a flowchart describing applicable clinical trials subject to FDA jurisdiction click 
here. 
 
Section 3: Publishing the results 
If yes to BOTH the study must be registered on Clinicaltrials.gov. 
Yes  
 
This study prospectively assigns people or a group of people to an intervention, 
with or without concurrent comparison or control groups, to study the cause-and-
effect relationship between a health-related intervention and a health outcome. 
 
The PI has access to and control over all the data from the clinical trial and has the 
right to publish the results of the trial and plans to publish the results in a journal 
that follows the ICMJE recommendations.  
This requirement includes studies of behavioral interventions. 
 
Section 4: Registration on Clinicaltrials.gov is not required 
Yes  
 
I have read sections 1-3 above and registration on clinicaltrials.gov is not required 
for this research.  
 
23) 
Criteria for 10 Year Approval  
If yes to all items below this research may qualify for a 10-year approval period. 
 
Yes  
 
This research involves no more than minimal risk. 
 
This research does not receive any federal or state government funding or funding 
from a private funder who requires annual review per contract. 
 
This research is not subject to FDA jurisdiction.  

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 12 of 13 
 
Revised: February 20, 2018 
 
This research does not include prisoners as participants. 
 
This research is not part of an IRB reliance. 
 
This research is not subject to SCRO oversight. 
 
This research is not subject to oversight by the Research Advisory Panel of 
California (RAP of C). 
 
This research does not involve personnel supported by federal training, center, or 
program grants. 
 
No personnel involved in the design, conduct, or reporting of this research have a 
financial interest (RFI) in this study. 
References 
1. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-
inflammatory drugs: network meta-analysis. Bmj 2011;342:c7086. 
2. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal 
antiinflammatory drugs. The New England journal of medicine 1999;340:1888-99. 
3. Abou-Raya S, Abou-Raya A, Helmii M. Duloxetine for the management of pain in 
older adults with knee osteoarthritis: randomised placebo-controlled trial. Age and 
ageing 2012;41:646-52. 
4. Chappell AS, Desaiah D, Liu-Seifert H, et al. A double-blind, randomized, placebo-
controlled study of the efficacy and safety of duloxetine for the treatment of chronic 
pain due to osteoarthritis of the knee. Pain practice : the official journal of World 
Institute of Pain 2011;11:33-41. 
5. Wise BL, Niu J, Zhang Y, et al. Psychological factors and their relation to 
osteoarthritis pain. Osteoarthritis Cartilage 2010;18:883-7. 
6. Kabat-Zinn J, University of Massachusetts Medical Center/Worcester. Stress 
Reduction Clinic. Full catastrophe living : using the wisdom of your body and mind 
to face stress, pain, and illness. New York, N.Y.: Delacorte Press; 1990. 
7. Hofmann SG, Sawyer AT, Witt AA, Oh D. The effect of mindfulness-based therapy 
on anxiety and depression: A meta-analytic review. Journal of consulting and clinical 
psychology 2010;78:169-83. 
8. Hilton L, Hempel S, Ewing BA, et al. Mindfulness Meditation for Chronic Pain: 
Systematic Review and Meta-analysis. Annals of behavioral medicine : a publication 
of the Society of Behavioral Medicine 2016. 
9. O'Leary K, O'Neill S, Dockray S. A systematic review of the effects of mindfulness 
interventions on cortisol. Journal of health psychology 2016;21:2108-21. 
10. Rosenkranz MA, Lutz A, Perlman DM, et al. Reduced stress and inflammatory 
responsiveness in experienced meditators compared to a matched healthy control 
group. Psychoneuroendocrinology 2016;68:117-25. 
11. Yadav RK, Magan D, Mehta N, Sharma R, Mahapatra SC. Efficacy of a short-term 
yoga-based lifestyle intervention in reducing stress and inflammation: preliminary 
results. Journal of alternative and complementary medicine 2012;18:662-7. 
12. MacCoon DG, Imel ZE, Rosenkranz MA, et al. The validation of an active control 
intervention for Mindfulness Based Stress Reduction (MBSR). Behaviour research 
and therapy 2012;50:3-12. 
13. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study 
of WOMAC: a health status instrument for measuring clinically important patient 

PROTOCOL TITLE: The Effect of Mindfulness Based Stress Reduction on Pain and 
Function in Persons with Knee Osteoarthritis 
 
Page 13 of 13 
 
Revised: February 20, 2018 
relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the 
hip or knee. The Journal of rheumatology 1988;15:1833-40. 
14. Gross JJ, John OP. Individual differences in two emotion regulation processes: 
implications for affect, relationships, and well-being. Journal of personality and social 
psychology 2003;85:348-62. 
15. Lange T, Vansteelandt S, Bekaert M. A simple unified approach for estimating 
natural direct and indirect effects. American journal of epidemiology 2012;176:190-5.