The Efficacy of Ultrasound Guided Posterior Sacroiliac Ligament Corticosteroid Injection in Pregnancy-Related Pelvic Girdle Pain: A Randomized Controlled Trial
Phase: PHASE2
Conditions: Pelvic Girdle Pain
Sponsor: Loyola University

 
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The Efficacy of Ultrasound Guided Posterior Sacroiliac Ligament Corticosteroid Injection 
in Pregnancy-Related Pelvic Girdle Pain: A Randomized Double Blinded Controlled Trial 
Colleen M. Fitzgerald, MD, MS (PI) (USA) 
Jean Goodman, MD (Maternal Fetal Medicine) (Co-I) (USA) 
Britt Stuge, PT, PhD (Co-I) (Norway)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revised Protocol – Version 4 
 
03-06-2015

 
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1. 
Protocol Synopsis  
1.1 
Study premise and specific research question 
Premise:  Pelvic girdle pain (PGP) in pregnancy is common with prevalence estimates of 45%.1 
It is defined as pain experienced between the posterior iliac crest and the gluteal fold, 
particularly in the region of the sacroiliac joint.2 Pain may radiate in the posterior thigh and can 
also occur in conjunction with/or separately in the symphysis. In PGP, the endurance capacity 
for standing, walking and sitting is diminished. The diagnosis of PGP can be reached after 
exclusion of lumbar causes and must be reproducible by specific clinical tests. While various 
pain mechanisms including mechanical, hormonal, inflammatory, and neural have been 
proposed in the development of PGP, the etiology and pathogenesis is poorly understood. It is 
possible that musculoskeletal changes influenced by hormonal (Relaxin) elevation in pregnancy 
predispose pregnant women to acute musculoskeletal injury presenting clinically as PGP. An 
inflammatory response in other acute musculoskeletal injuries has been well described3 and 
may also occur in pregnancy related PGP particularly given the musculoskeletal vulnerability 
during this time. Though PGP is common in pregnancy, no study to date has investigated the 
efficacy of anti-inflammatory treatment in pregnancy related PGP in order to better establish the 
contribution of inflammation in the etiology of pregnancy related PGP. 
Specific research question: 
Can pregnancy related PGP be more effectively treated with the use of injectable anti-
inflammatory medication plus lidocaine compared with a saline with lidocaine active comparator 
injection? 
1.2 
Specific study objectives 
Primary question and response variable:  

 
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Does ultrasound guided posterior sacroiliac ligament corticosteroid injection combined with 
lidocaine provide superior pain relief in pregnant women with PGP in the second or third 
trimester compared with a saline with lidocaine active comparator injection as measured by the 
pain Numeric Rating Scale (NRS) (0-10)?  
Primary outcome variables: Pain NRS (0-10) (anchors: 0 = none, 10 = worst imaginable) 
Secondary questions and response variable: 
Does posterior sacroiliac ligament corticosteroid injection combined with lidocaine in pregnant 
women with PGP in the second/third trimester result in less disability and improved physical 
examination as compared with a saline with lidocaine active comparator injection? 
Secondary outcome variables: Oswestry Disability Index (ODI), Pelvic Girdle Questionnaire 
(PGQ) and physical examination testing including the Patrick’s Faber test, the Posterior Pelvic 
Pain Provocation test (PPPP or P4), long dorsal ligament (LDL) palpation, pubic symphysis 
palpation, the modified Trendelenburg test and the Active Straight leg raise (ASLR) test. 
1.3 
Summary of the study design 
Study design: Randomized double blinded controlled trial.  
Power calculation:  Sample size (total and in each treatment group): A minimum of 50 
participants, 25 in each treatment group would be sufficient to detect a treatment effect of a 2 
point change in NRS at the 4 and 8 week follow-up period with 80% power at a 5% significance 
level (two tailed). 5 patients will be added to each group to account for a 10% loss to follow-up 
rate. 
Population: Clinic-based patients seen at the at the Loyola University Medical Center, Gottlieb 
Hospital Obstetrics Clinics or patients referred from Chicagoland area hospitals or physical 
therapy practices 
Intervention Group:  Ultrasound guided posterior sacroiliac ligament corticosteroid plus 
lidocaine injection  
Control Group: A saline with lidocaine active comparator injection  

 
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Follow-up: Conducted at 7 days, 4 weeks, 8 weeks and 6 weeks postpartum after intervention 
Primary Outcome measure: Pain Numeric Rating Scale (NRS) (0-10) 
Secondary Outcome measures: ODI, PDQ, and physical examination testing 
2. 
Rationale 
Pelvic girdle pain (PGP) often described by patients as “sciatica” is an important problem in 
pregnancy that can lead to significant functional disability4, postpartum chronic pelvic pain5, 
depression6 and adversely affect future child-bearing decision making7.  Current treatment 
utilizes physical therapy (PT) with stabilizing exercises and this is supported by the literature8,9. 
Clinically, however, there is often a group of severe pain patients (often those with pelvic girdle 
syndrome, i.e. bilateral sacroiliac joint and pubic symphysis pain) that do not respond to 
physical therapy alone and have the poorest prognosis10,11. These are the same patients who 
typically go on to persistent postpartum chronic PGP. Optimal pain relieving treatment in 
pregnancy could possibly prevent chronic PGP postpartum and the significant long-term 
disability associated with it. 
2.1 
Research to date 
Randomized clinical trials on exercise/physical therapy interventions12,13, acupuncture14 
and an educational intervention15,16 have been performed in the study of PGP during pregnancy. 
There are currently no randomized clinical trials, however, evaluating the use of pain 
medications or corticosteroids for PGP in pregnancy. Torstensson et al performed a randomized 
double blind controlled trial evaluating the use of intravaginal corticosteroid injection at the 
ischiadic spine in postpartum women with persistent sacral pain. Slow release triamcinolone 
and lidocaine provided superior pain relief compared with saline and lidocaine alone.17 
Musculoskeletal ultrasound (US) has been widely utilized in other musculoskeletal joint 
disorders to diagnose pathology 18 and recently to identify the posterior sacroiliac joint 
ligamentous structures19.  It has also been used to evaluate the sacroiliac joint in the non-

 
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pregnant state for the purpose of diagnostic (anesthetic) joint injection with good success 20. US 
is already routinely being performed for obstetrical use during pregnancy and is considered safe 
in pregnancy due to its lack of radiation exposure 21.  
Glucocorticoids constitute one of the most frequently prescribed medications during 
pregnancy, used commonly in preeclampsia and for maternal inflammatory, dermatologic, and 
autoimmune disorders. Antenatal glucocorticoids are used for a multitude of reasons in 
pregnancy. Examples of use are asthma refractory to inhalant therapy (National Asthma 
Education and Prevention Program: Full Report of the Expert Panel: Managing asthma during 
pregnancy: Recommendations for pharmacologic treatment – 2004 update. NHLBI, NIH 
publication no. 005-3279l), autoimmune disorders22,23 and for acceleration of fetal lung maturity 
for women at risk of preterm birth24. 
Although fluorinated glucocorticoids are known to cross the placenta readily, the majority 
of prednisone and methylprednisolone (non-fluorinated glucocorticoids) are inactivated in the 
placenta and do not reach the fetus in significant concentrations. Both of the latter are Category 
C agents in that animal studies show no risk but no definitive studies in humans have been 
done, and may be safely used as anti-inflammatory/immunosuppressive agents if indicated in 
pregnancy25.  
3. 
Protocol (See Appendix II and III) 
Patients will be approached in their second or third trimester regarding the study in the 
Obstetrics or Rehabilitation clinics if they have PGP. They will be given a flyer regarding the 
study. If interested in participating, they will either proceed to study visit 1 (baseline), if time 
permits, or set up a separate time for study visit 1 to take place. Patients will be consented and 
evaluated for eligibility at this baseline visit. Eligible patient will be randomized to either the 
control or intervention groups at study visit 1. They will receive the injected medication at study 
visit 1. This study will require study visits total, study visit 1 will be at the time of randomization, 

 
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study visit 2 will be 4 weeks after injection, study Visit 3 will be at 8 weeks after start of 
intervention/after injection. and study visit 4 will be 6 weeks post-delivery. There will be one 
follow-up phone call between visit 1 and 2 on day 7 following intervention to inquire about any 
medication side effects or adverse events.  Study duration is 8 weeks per patient, with an 
expected two year total recruitment and data collection time period. At study visit 1, patients will 
be randomized to receive the intervention medication or active comparator and undergo a 
physical examination of the external musculoskeletal pelvis and will complete the NRS for ‘worst 
pain’ and ‘mean pain’ during the latest 48 hours, a pain diagram, a personal health information 
questionnaire regarding their pregnancy, past medical history, activity level and restrictions. 
Disability as measured by the Pelvic Girdle Questionnaire (PGQ) and Oswestry Disability Index 
(ODI), Health-Related Quality of Life (HRQL) measured by the Wellbeing NRS and work ability 
will be measured with one question from Workability Index i.e. “Current work ability compared 
with the lifetime best”. 
Those randomized to the will receive either 40mg of a non-fluorinated injectable 
glucocorticoid, methylprednisolone acetate (1cc) combined with 1cc of 1% Lidocaine or 1cc f1% 
Lidocaine plus 1cc of normal saline. The injection will be performed unilaterally if pain is single 
sided or bilaterally if the pain is in both sacroiliac joint regions The injection will be ultrasound 
guided and performed by the PI Dr. Fitzgerald who is trained in musculoskeletal ultrasound and 
ligamentous injections as a specialist in physical medicine and rehabilitation. Dr. Fitzgerald and 
the participant will both be blinded to the type of injectate used. Study visits 2 and 3 will include 
the same questionnaires and physical examination and will document any change in the 
pregnancy status. Study visit 4 will occur 6 weeks post-delivery and will include the same 
questionnaires and physical examination to determine if any chronic pain remains. Patients will 
be allowed to utilize acetaminophen as needed and the amount utilized in each intervention arm 
will be recorded. Total study visit time is expected to be 60 minutes for study visit 1 and 30 
minutes for visits 2-4. Standard physical examination maneuvers validated for the assessment 

 
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of pregnancy related PGP will be performed by the PI Dr. Fitzgerald and include pelvic pain 
provocation tests and functional stability testing. It will be noted with each maneuver whether 
the test was positive or negative. They will include: 
a. Patrick’s Faber test:  With the patient in supine, the patient’s leg is flexed, abducted and 
externally rotated so that the heel rests on the opposite kneecap. This test is positive with 
production of pain in the sacroiliac joint.  
b. Posterior Pelvic Pain Provocation (P4) test: with the patient supine, the femur is flexed to be 
perpendicular with the table at 90 degrees and the knee is flexed at 90 degrees.  A gentle force 
is applied to the femur in the direction of the examination table. The test is positive when the 
patient experiences pain in the gluteal region of that leg.  
c. Long Dorsal Sacroiliac Ligament (LDL) palpation test: The subject lies on her side with slight 
flexion in both hip and knee joints. Specifically, the LDL is palpated directly caudomedially from 
the posterior iliac spine to the lateral dorsal border of the sacrum if palpation causes pain that 
persists five seconds after removal of the examiner’s hand, it is recorded as pain. If the pain 
disappears within five seconds, it is recorded as tenderness. When the identical pain is felt 
directly in the vicinity, but outside the borders of the ligament, the test is not deemed as positive.  
d. Pubic Symphysis palpation test: Examiners will palpate the subject’s pubic symphysis joint 
while the patient is lying supine for tenderness. If palpation causes pain that persists five 
seconds after removal of the examiner’s hand, it is recorded as pain. If the pain disappears 
within five seconds, it is recorded as tenderness. 
e. Modified Trendelenburg’s test: The standing woman stands on one leg and flexes the other at 
90° (hip and knee). The test is considered positive if pain is experienced in the symphysis.  
f. Active Straight Leg Raise (ASLR) test: performed with the patient supine with straight legs 
extended on the table 20 cm apart.  The patient raises each leg one at a time 20 cm above the 
table without bending the knee.  A) The test is positive when the patient describes a heaviness 
or difficulty in performing the task.  B) In the second part of the maneuver, posterior 

 
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compression is applied and the patient is then asked to actively perform a straight leg raise.  If 
there is greater ease in lifting the leg this is considered a positive test.  The patient will be asked 
to score impairment (scoring inadequacy to raise the legs but not pain) on a 6-point scale: not 
difficult at all = 0, minimally difficult = 1, somewhat difficult = 2, fairly difficult = 3, very difficult = 
4, unable to do = 5, the scores of both sides will be added so that the summed score can range 
from 0-10. Impairment is considered severe if the summed bilateral score is at least 4.  
Personal Health Information to be collected  The personal health information (PHI) items that 
will be collected during pregnancy will include:  name, phone number; date of birth; BMI; height; 
age; race; education level; income level; number of previous pregnancies; number of previous 
deliveries; types of previous deliveries, past abdominal surgeries if any, current medications; 
history of other pain diagnoses, history of depression; history of neurological disease; history of 
anxiety; history of sexual abuse; previous low back injury; previous low back or pelvic pain; 
history of smoking; history of infertility; history of urinary or fecal incontinence; history of 
interstitial cystitis; history of arthritic conditions (osteoarthritis, rheumatoid arthritis, lupus); body 
parts affected by arthritic conditions; diabetes (Type I, Type II, gestational); gestational week of 
current pregnancy; due date of current pregnancy; number of babies expected; 
trimester/gestational week of onset of low back and/or pelvic pain (if applicable); current 
pregnancy complications; occurrence of miscarriage; activity and exercise types and levels 
during pregnancy; activity level restrictions; and duration for any previous physical therapy; 
previous home exercise program; and physical therapy descriptions and reasons for initiating 
therapy after enrollment in the study. Social history including marital status, support at home, 
and type of occupation will be documented. 
3.1  
Eligibility criteria: 
 
English speaking pregnant women presenting in their second or third trimester with 
posterior PGP.  Trimester will be determined from date of last menses or ultrasound 
date.  

 
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 
Women who have failed physical therapy for pain management  (physical therapy, 
chiropractic management, aquatic therapy 
 
Pain NRS on average of greater than or equal to 5/10 at Visit 1  
 
Pain must be between the upper level of the iliac crests and the gluteal folds in 
conjunction with or separately from pain in the pubic symphysis and influenced by 
position and locomotion 
 
2/4 positive physical examination tests on the symptomatic side including the P4 test, 
the LDL test, pubic symphysis palpation and the ASLR  
3.2  
Exclusion criteria: 
 
Non-English speaking pregnant women <21 or >50 years old  
 
Women presenting with PGP in the first trimester (<13 weeks gestation) 
 
Women with pubic symphysis (anterior) pain alone 
 
Women who have not yet received some form of physical therapy for their pain 
 
Pain above the upper level of the iliac crest 
 
History of lumbar or pelvic fracture, neoplasm, inflammatory disease, active urogenital 
infection or active gastrointestinal illness, current physical therapy or other therapies for 
PGP, or previous surgery of the lumbar spine, pelvic girdle, hip joint or femur   
 
History or signs of radiculopathy or other systemic neurologic disease  
 
Women with diabetes or gestational diabetes 
3.3 
Intervention 
Experimental intervention: At the posterior sacroiliac joint ligament just inferior to the posterior 
superior iliac spine, 40mg of methylprednisolone acetate (1cc) combined with 1cc of 1% 
Lidocaine will be injected using a 1.5 inch 25 gauge needle. The medication with be injected 
unilaterally if pain is single sided or bilaterally for a total of 4cc of medication if the pain is in both 

 
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sacroiliac joint regions. The subject will subsequently receive once weekly physical therapy for 4 
weeks. 
Control intervention: At the posterior sacroiliac joint ligament just inferior to the posterior 
superior iliac spine, 2cc of saline with 1cc of 1% Lidocaine will be injected using a 1.5 inch 25 
gauge needle. The medication with be injected unilaterally if pain is single sided or bilaterally for 
a total of 4cc of placebo saline if the pain is in both sacroiliac joint regions.  
The subject will subsequently receive once weekly physical therapy for 4 weeks 
3.4 
Consent process 
Patients will be identified when they arrive for a scheduled MD appointment at any point during 
their second or third trimester. They will be given a flyer with information about the study and will 
be asked to participate A separate study visit 1 time will then be scheduled. At study visit 1, if 
the patients meet eligibility criteria, a consent form will be read to them describing the nature of 
the trial and potential associated risks and benefits.  They will be informed that neither 
participation nor refusal will influence the care received at either Loyola University Medical 
Center or Gottlieb Hospital. They will be asked a few questions afterwards to verify 
comprehension and then sign the consent form documenting their agreement to participate.  A 
copy of the consent form will be given to them.  Participation is completely voluntary and they 
may discontinue participation in the study at any time.  Patients will complete the informed 
consent process at study visit 1.  A study coordinator (Mary Tulke) or the PI (Dr. Fitzgerald) will 
consent all patients. The patients who consent to participate will be given a set of 
questionnaires at that time and asked to complete them during study visit 1. Consenting patients 
will undergo systematic examination procedures. These procedures will be performed by the PI. 
Patients will receive parking vouchers for each study visit.  
3.5 
Trial design 
Randomized double blinded controlled clinical trial 
3.5.1 Pre-Enrollment 

 
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Eligible participants will be informed about this trial during any second or third trimester visit 
when they complain or present clinically with PGP in the office. Special efforts will be made to 
increase enrollment in certain subgroups (minorities). No other medical or other documentation 
will required for determining eligibility. After assuring eligibility, patients may proceed to study 
visit 1 where consent and randomization will take place. With prevalence rates of PGP in 
pregnancy at 45%, there will be ample availability of eligible participants. Sixty total participants 
will be enrolled. 
3.5.2 Randomization 
Randomization strategy will be developed in collaboration with Loyola Biostatistics Department, 
using blocks of 3 stratified on pain location and allocation will be a 1:1 ratio of patients in the 
intervention and control groups. The randomization procedure will take place at study visit 1 
after informed consent is completed and eligibility status is determined.  A research coordinator 
(Mary Tulke) blinded to the study will give precoded identical envelopes with randomization 
assignments to the patients at the conclusion of study visit 1. This assistant and an independent 
Data and Safety Monitoring Board (DSMB) will have access to the randomization code.  
3.5.3 Intervention administration 
The injection intervention will be administered at study visit 1 following successful recruitment 
and consent. Since physical therapy is considered standard of care treatment in the 
management of pregnancy related PGP, all participants will need to have failed PT. 
3.5.4 Follow-up 
Patients will be instructed to contact the study nurse coordinator blinded to the study 
hypotheses with any side effects: flushing, nausea, vomiting, insomnia, and/or worsening pain 
at any time during the first week. The study nurse coordinator will then contact each patient by 
phone on day 7 after the injection regarding medication tolerance. After the four weeks of 
physical therapy, patients will return for a repeat questionnaire administration and physical 
examination. Questionnaires will be performed prior to physical examination so as not to 

 
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influence pain scores. During the course of physical therapy, they will be reminded by the 
physical therapist to follow-up with study visit 2 and reminder letters mailed the week prior to 
study visit 2.  Study visit 3 will be performed eight weeks post injection to determine if the 
intervention has a lasting effect. Study visit 4 will occur 6 weeks post-delivery and will include 
the same questionnaires and physical examination to determine if any chronic pain remains. 
3.5.5 Adverse event reporting* 
The PI or the study nurse coordinator can be reached by pager or phone and will be on call for 
study patients 24 hours a day. Dr. Jean Goodman, chief Loyola Maternal Fetal Medicine will 
also be available for patient adverse reactions. Adverse events to be recorded will include 
excessive bleeding, infection, significantly worse pain at the 7 day post-injection phone check, 
fetal distress or demise, fall post injection, and/or maternal hospital admission. If the subject has 
persistent post injection side effects of flushing, nausea, vomiting or insomnia, this will be 
reported. If any other unanticipated adverse event occurs, this will also be immediately reported 
to the IRB. A data safety monitoring plan is detailed below in the section titled “Safety 
Monitoring Plan.” 
3.5.6 Confidentiality 
Following HIPPA guidelines, patient identifiable data will be coded to protect each patient’s 
identity.  The data obtained from the patients will be entered onto electronic forms and imported 
into the database. We are familiar with using this technology from other studies. It is efficient to 
complete in a clinical setting and minimizes data entry errors. The data will be presented in peer 
reviewed manuscripts and other public presentations at the group level only. No individual 
patients will be identified.  
3.6 
Schedule of events  
(Refer to Appendix I for schedule of events, Appendix II for study timeline and to Appendix IV for 
study forms, attached pdfs) 
3.7 
Sample size (Refer to Appendix III for calculations) 

 
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Sample size calculations are based on a 2-sided type I error rate of .05 and 80 % power.  An 
additional 10% is added to account for loss to follow-up and for premature deliveries.  Non-
compliance is expected to be minimal given the short duration of the study medication 
intervention. The variance estimates are obtained from a previously reported RCT in pregnancy 
related PGP by Bastiaenen16.  Approximately 50 participants will be needed to detect 2-point 
NRS effect size for 25 (exp) compared to 25 (control).   
3.8 
Analysis 
Data will be analyzed using descriptive univariate statistics with STATA 11.0. In this population, 
there is evidence from current literature that pain and disability may not be normally distributed.  
If this is the case, the primary and secondary outcomes, pain and disability respectively, will be 
presented as median values and interquartile ranges.  Comparisons between the intervention 
groups at follow-up will be performed using the Mann Whitney U test and change within groups 
from baseline to follow-up will be examined using the Wilcoxon signed-rank test. If data are 
sufficiently normally distributed and differences are found, multivariate analyses will be 
conducted. This will determine the need to control for group differences based on location of 
pain, history of low back pain or pelvic girdle pain, age, educational level, parity, and time from 
pain onset. Additional secondary analyses will examine the impact of the treatment group 
assignment on physical examination tests using chi-square test of proportions. 
4. 
Risks and Benefits 
The excellent overall safety and efficacy record of injectable corticosteroids is well 
established26. A prospective evaluation of intraarticular and periarticular injections with 
methylpredinisolone found a very low rate of complications27. Systemic effects of injectable 
corticosteroids are influenced by the agent used, dose, frequency and number of sites injected. 
Osteoporosis is found only with use of systemic/oral steroids and myopathy more commonly 
documented with oral fluorinated steroid use has not been reported with intraarticular injections. 
The ability of intraarticular injections to suppress the hypothalamic pirutitarty-adrenal (HPA) axis 

 
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is well documented28 but has not been described with extraarticular or ligamentous injections. A 
corticosteroid induced increase in glucose synthesis is not seen in soft-tissue injections of 
methylprednisolone acetate29.  
Fetal Risk and Benefit 
Glucocorticoids constitute one of the most frequently prescribed medications during 
pregnancy, used commonly in preeclampsia and for maternal inflammatory, dermatologic, and 
autoimmune disorders. Antenatal glucocorticoids are used for a multitude of reasons in 
pregnancy. Examples of use are asthma refractory to inhalant therapy (National Asthma 
Education and Prevention Program: Full Report of the Expert Panel: Managing asthma during 
pregnancy: Recommendations for pharmacologic treatment – 2004 update. NHLBI, NIH 
publication no. 005-3279l), autoimmune disorders22,23and for acceleration of fetal lung maturity 
for women at risk of preterm birth24. 
Although fluorinated glucocorticoids are known to cross the placenta readily, the majority 
of prednisone and methylprednisolone (non-fluorinated glucocorticoids) are inactivated in the 
placenta and do not reach the fetus in significant concentrations. Both of the latter are Category 
B agents in that animal studies show no risk but no definitive studies in humans have been 
done, and may be safely used as anti-inflammatory/immunosuppressive agents if indicated in 
pregnancy25.  
In light of this, the investigators feel that there is minimal risk to the fetus. Fetal exposure 
to systemic corticosteroids in pre-term labor and been proven safe and even advantageous to 
fetal lung maturity. There is no benefit in this study to the fetus aside from the potential long 
term benefit of better maternal pain control in the postpartum period that would influence 
maternal-child bonding and childcare.  
Maternal Risk and Benefit:  
 
The risk to the mother is also minimal. Mothers with moderate to severe pain have 
significant disability that affects current and future quality of life. The potential benefit of the pain 

 
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treatment outweighs the minimal risk. Both study groups will receive standard of care physical 
therapy (cost covered by their insurance), a proven treatment for pregnancy related pelvic girdle 
pain. For the intervention group that receives methylprednisolone, expected immediate side 
effects might include vasovagal reaction and delayed (2 days) side effects might include 
injection site soreness, sweating or facial flushing30. Toxicity at high levels and multiple dosing 
effects are not expected given that this is a low dose of corticosteroid injected locally. Infection 
rates associated with injection are low and typically seen in intraarticular not extraarticular 
injections31. A possible rare adverse effect might include allergic reaction. If an adverse reaction 
or side effect occurs, the subject will be seen by Dr. Goodman (maternal fetal medicine) at 
Loyola. This will also be immediately reported to the IRB. 
The benefits of the intervention include the possibility of superior pain relief compared 
with placebo. Lidocaine has been safely and successfully used in pregnant women undergoing 
amniocentesis.32 Oral steroids are used for other conditions in pregnancy such as asthma, 
rheumatoid arthritis, and severe sinusitis. They are also utilized in the treatment of pre-term 
labor to assist in the development of fetal lung maturity. Methylprednisolone is a class B drug 
and its well-established clinical utility in other diseases lends to the safety of its potential use in 
this debilitating pain condition (PGP) in pregnancy and warrants further study for the treatment 
of musculoskeletal pain. 
I. 
Safety Monitoring Plan 
a. Definition of adverse events, serious adverse events 
i. An adverse event is defined as any symptom or medical problem 
experienced by the participant following consent to participate.  All adverse 
events must be reported to the study physician and regulatory coordinator 
within three working days of discovery.  All adverse events that occur during 
the trial will be recorded on the adverse event log.  The investigator study 
physician will ask patients at each visit “Have you experienced any 

 
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symptoms or medical problems since your last visit?” and will subsequently 
record all events using the adverse event log. 
ii. Serious adverse events must be reported to the University’s IRB, Principal 
Investigator, Study Physician, and Regulatory Coordinator within 24 hours of 
discovery using the Serious Adverse Event Case Record Form.  An SAE is 
defined as any adverse drug experience that results in: 
1. Death 
2. A life-threatening adverse experience 
3. An important medical event 
4. Inpatient Hospitalization (or prolonged hospitalization) 
5. Persistent or significant disability/incapacity 
6. A congenital anomaly or birth defect  
iii. Finally, the principal investigator or her designee will record on the adverse 
event log:  (1) A description of the event, (2) the start date of the event, (3) 
the stop date of the event, (4) the expected relationship to the study drug, 
(5) Whether any action was taken with the study drug, and (6) the primary 
outcome of the event.  Additionally, the principal investigator or her designee 
will record any change in an ongoing adverse event. 
b. What procedures will be used to monitor subject safety? 
i. All participants will complete a general physical examination prior to 
randomization.  Data will be recorded using the General Physical Case 
Record Form. 
ii. Vital signs (weight, height, temperature, seated blood pressure, and seated 
heart rate) will be taken at each visit.  Data will be recorded using the Vitals 
Case Record Form. 

 
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iii. [Description of labs used to monitor mother and child health, and how often 
those labs will be collected and evaluated.  Also describe whether the 
participant will receive a copy of their laboratory results, and whether such a 
report will be given directly to them or sent to their personal healthcare 
provider]. 
iv. Participants are encouraged to report any (1) New adverse event, (2) 
whether any existing adverse events have worsened or resolved, (3) 
whether there are any changes to their concomitant medications, and (4) 
whether a medication was required to treat an adverse event.  Such 
information is recorded on the adverse event log CRF and concomitant 
medication log CRF as necessary. 
c. Who (list names) will identify, document, and report adverse events? 
i. All named research members may receive information about an adverse 
event and, consequently, are required to report such events as described in 
this protocol. 
ii. The principal investigator and/or study physician will evaluate (1) The 
expected relationship of the event with the study drug and (2) Whether any 
action should be taken regarding the study drug following an adverse event. 
d. What is the frequency for review of summarized safety information and 
who will perform the review (e.g., safety monitoring board)? 
i. The Principal Investigator or her designee will alert Loyola University 
Chicago Health Sciences Division IRB#1 promptly of all serious and any 
unexpected adverse events associated with the project (or the study 
supplement).  Associated is defined as any adverse experience that is 
possibly, probably, or definitely related to the study drug.  Unexpected is 

 
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defined as any untoward experience following informed consent that is not 
listed as a risk in the informed consent document. 
ii. The Principal Investigator will also promptly report non-compliance with the 
activities described in the protocol, participant complaints, and any billing 
errors.  Additionally, the PI will promptly report: 
1. Serious adverse events (including events that produce injury or 
death, an event leading to hospitalization or lead to prolongation 
of a current hospital stay) 
2. The enrollment of a patient on a study that is no longer enrolling 
participants 
3. Any patient reporting a billing problem as a result of project 
participation 
4. Any participant who has voiced a complaints about some aspect 
of the project or the consent document 
5. Any unanticipated, untoward, or unexpected adverse event not 
covered above including rare adverse events or adverse events 
that occur at an unexpected rate 
6. Protocol deviations 
7. Investigational drug/device brochures and revisions 
e. What are the stopping rules with regard to efficacy and safety? 
i. A decision to stop the study may be made when there are documented 
serious maternal or fetal adverse events that can be possibly, probably, or 
definitely attributed to study drug exposure and are deemed to exceed the 
potential benefits of the study drug. 
ii. The principal investigator, the Institutional Review Board, or United States 
Government Regulatory Authorities (e.g., the Federal Drug Administration or 

 
Protocol Version 4 – 03-06-2015 
 
 
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FDA) may stop this study at any time.  If this happens, the research team 
will be in direct contact with the Institutional Review Board and regulatory 
agency regarding participants’ suspension or termination of study drug. 
iii. The investigator may decide to stop a subject’s participation in this trial at 
any time.  This may happen, for example, if the participant fails to comply 
with the protocol activities or experiences an adverse event.  If this happens, 
the research team will be in direct contact with the Institutional Review 
Board and will, with the participant’s informed consent, continue to follow the 
participant off study drug for pregnancy outcome and fetal adverse events. 
 
5. Importance of Clinical Research in Pregnant Women 
 
In October 2010, the Office of Research on Women’s Health (ORWH) convened a 
scientific research forum, Issues in Clinical Research: Enrolling Pregnant Women in partnership 
with several National Institutes of Health (NIH) institutes, centers, offices and the Food and Drug 
Administration (FDA), to address the ethical/ Institutional Review Board (IRB) and recruitment 
issues that investigators face in the conceptualization, initiation, and conduct of clinical research 
studies that enroll pregnant women. During this forum, the audience was challenged to address 
gaps in knowledge about medical treatment and pregnancy, to increase the evidence base on 
the inclusion of pregnant women in clinical research, and to conduct appropriate scientifically-
and ethically-designed clinical research. Medical ethicists, clinical investigators, academic 
researchers, and those with an interest in and concern about clinical research in women 
provided information related to risk perception, risk reasoning, and the ethics of balancing risks 
and benefits in the clinical arena. 
 
The NIH strategic plan for research on women’s health identified six major goals for 
women’s health research, one of which was the goal of increasing research to “actualize 
personalized prevention, diagnostics and therapeutics for girls and women.” Among specific 

 
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objectives listed for the goal were two objectives that directly addressed pregnancy: 1) 
“encourage research on safe and effective interventions for conditions affecting pregnant 
women”; and 2) “expand research on pregnancy related conditions, such as preeclampsia, 
diabetes, and hypertension on the subsequent health of women and their offspring.” 
 
The report from this forum (http://orwh.od.nih.gov/resources/policyreports/pdf/ORWH-
EPW-Report-2010.pdf) made several poignant statements relevant to Dr. Fitzgerald’s proposed 
project.  
 
“The current approach to treatment during pregnancy has resulted in significant 
knowledge gaps and harms. Pregnant women are left with two unacceptable options: 
either take a drug of unknown safety and efficacy or fail to treat a condition, with 
consequences. Pregnant women deserve better.”  
 
 “Only 12 drugs are explicitly approved by the FDA for use in pregnancy. These drugs 
are approved either to prevent premature labor or to ameliorate labor pain. All medicines 
used for non-obstetrical treatments with pregnant women are off-label. Pregnancy is the 
ultimate off-label condition. This lack of knowledge has led to a profound reticence to 
treat pregnant women when they do fall seriously ill, and it ends up harming the women 
and the babies.”  
 
“What is needed in the case of pregnancy research is the development of a thoughtful, 
careful framework to address a scientifically and ethically challenging situation.”  
 
 
The PI (Dr. Fitzgerald) and co-investigators of this proposed project (Drs. Goodman, 
Loyola chief of maternal fetal medicine) and Dr. Stuge (scientific collaborator and international 
expert in pregnancy related PGP RCTs) feel strongly that the proposed study addresses a 
significant issue in pregnancy: disabling pelvic girdle pain that can lead to deleterious maternal 
consequences if left untreated. We feel the injectate proposed is safe and with ultrasound 
guidance will pose minimal risk to the mother and fetus. The potential significant maternal 

 
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benefit outweighs this minimal risk. The proposed study also is in response to the NIH call to 
action for clinical research in pregnancy. The study has already been peer reviewed by the 
American Academy of Physical Medicine and Rehabilitation Foundation and, given its potential 
significant scientific contribution, has already been funded with recruitment to start in 2014. 
 
 

 
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Appendix I:  Schedule of procedures/ Study Schedule  
Visit Number 
 1 
(baseline) 
Day 0 
 2 
Day 7 
3 
4 weeks 
4  
8 weeks 
5 
6 weeks 
postpartum 
Consent  
X 
 
 
 
 
Randomization 
X 
 
 
 
 
Intervention 
X 
X 
 
 
 
Physical Exam 
X 
 
X 
X 
X 
Questionnaires 
X 
 
X 
X 
X 
Phone f/u 
 
X 
 
 
 
Participation: 8 weeks per patient, anticipate one year of recruitment  
Appendix II:  Sample Size Calculations 
Sample size was determined under the assumption that a difference of 2 on NRS would have 
clinical relevance. This was based on the previous work of Elden14 in an RCT for acupuncture 
compared with sham for PGP in pregnancy. The 2 point  difference on the NRS has also been 
used in other gynecologic RCTs in the measurement of pain.33 The standard deviation of 25 mm 
was derived from the prior work of Bastiaenen16 in an RCT comparing a specific educational 
physical therapy program to usual care in postpartum PGP. No standard deviations were 
available in the Elden paper or in any other literature on this topic. For the primary outcome of 
patient pain ratings (0-10 NRS) after 4 weeks of physical therapy with or without 
methylprednisolone, a sample size of 50 (25 in each group) will give the study 80% power to 
identify a 2 point difference on the NRS (with [alpha] of .05). The 4 week follow-up time period is 
used because the clinical effect of the study medication is expected within the 4 weeks. An 
additional 5 participants in each group is added to account for a loss to follow-up of 10% which 
calculates to then 30per treatment group. Power analyses were performed by using STATA 

 
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11.0. The basic formula for calculation is Δ/σ = 3.96/√n, with Δ = effect size, σ = the standard 
deviation and n = number of patients needed. 
 
Sensitivity analysis  
Expected change in NRS (Effect size) 
N if Power 80% 
N if Power 90% 
1 
198 (99 per group) 
264 (132 per group) 
1.5 
88 (44 per group) 
118 (59 per group) 
2 
50 (25 per group) 
66 (33 per group) 
3 
22 (11 per group) 
30 (15 per group) 
 
 
 

 
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