Clinical trial NCT03604341
Conditions: Medical Abortion Pain
Keywords: Medical Abortion Pain Cannabis
Sponsor: Oregon Health and Science University
Start date: 2018-11-01; Completion date: 2019-05-28
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of this study is to determine if a synthetic cannabis derivative, dronabinol, in addition to ibuprofen, decreases maximum pain scores compared to ibuprofen and placebo in women undergoing medical abortion. Results of this study will help providers counsel patients regarding cannabis use during medical abortion.

Detailed description:
This is a randomized, double-blind, placebo-controlled trial comparing pain levels in women undergoing medical abortion with one of two regimens: ibuprofen 800mg and a 5mg oral dronabinol versus ibuprofen 800mg and placebo given at the time of misoprostol administration. This study will include 62 women undergoing medical abortion. Women will be randomized to dronabinol 5mg oral versus placebo. The primary outcome will be maximum reported pain score within 24 hours of misoprostol administration.

Arms: arm 1: Women with gestational age up to 10 weeks 0 days will be randomized to Dronabinol 5mg Cap or placebo arm 2: Women with gestational age up to 10 weeks 0 days will be randomized to Dronabinol 5mg Cap or placebo
Interventions: intervention 1: Dronabinol 5mg Cap intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects randomized to Dronabinol 5mg Cap and ibuprofen 800mg for pain intervention 2: Subjects randomized to placebo and ibuprofen 800mg for pain

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
Official Title: Cannabinoids for Pain Control during Medical Abortion 
 
 
 
 
Principal Investigator: Katie Alton, MD, MCR 
 
 
 
 
NCT No. 03604341 
 
 
 
Protocol Version Date: 06 March 2019 
 
 
 
 


 
 
 
 
 
1. Protocol Title 
Cannabinoid Analgesia for Medical Abortion: A Randomized Controlled Trial 
 
2. Objectives 
Objective 
To compare the reported maximum pain score within 24 hours of induced medical abortion 
of women who receive cannabinoids and ibuprofen compared to ibuprofen and placebo 
using an 11-point numeric rating scale (NRS) (0-10). Pain levels will be collected 
prospectively via text message at hours 0 (misoprostol administration), 6, and 24 hours, 
and maximum pain score and timing during the preceding interval will be recorded. 
 
Hypothesis 
Women undergoing medical abortion up to 10 0/7 weeks who receive cannabinoid 
analgesia and ibuprofen will report lower maximum pain scores compared to ibuprofen 
alone. 
 
Primary Outcome 
Maximum self-reported pain score on a NRS during the 24 hours after administration of 
misoprostol.  
 
Secondary Outcomes 
1. Maximal pain score. (We have powered our study in order to have sufficient sample size 
for this secondary outcome).  
2. Pain level at time of participant-reported expulsion using NRS.  
3. Proportion of women reporting a maximum pain score >7. 
4. Number of capsules of study drug and ibuprofen tablets used during the 24 hours after 
administration of misoprostol. 
5. Use of additional medications.  
6. Presence of nausea/vomiting within 24 hours. 
7. Participant satisfaction with pain management.  
8. Need for additional pain medications between mifepristone ingestion and follow up 
appointment. 
9. Number of calls to the clinical advice line, as documented in the eletronic medical record. 
10. Adequacy of blinding: “Do you believe you took the study drug or a placebo?” 
11. Adverse events. 
 
3. Background 
In 2011, nearly half (45% or 2.8 million) of the 6.1 million pregnancies in the United States 
were unintended [1], with an abortion rate of approximately 17 per 1,000 women [2]. 
Medical abortions account for approximately 31% of all abortions [3]. As a safe and 
efficacious alternative to surgical abortion, rates of medical abortion continue to rise relative 
to surgical abortion [4]. However, pain and anxiety during medical abortion continue to be 
significant issues and potential barriers to care. Abortion-related pain has not been 
systematically studied in clinical trials, limiting our ability to recommend appropriate 
analgesia [5]. Medical abortion has been described as painful in 36-86% of patients [6-8], 
with up to one-third of women reporting more pain than anticipated and unacceptable 
maximum pain scores [6]. 
 


 
 
 
 
 
Currently, nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of analgesia 
regimens for abortion-related pain. However, NSAIDs do not provide sufficient pain relief 
for many women in the setting of medical abortion, with almost half of patients reporting 
maximum pain scores between 8-10 on an 11-point numeric rating scale [9]. To supplement 
ibuprofen, some providers offer opioids but no consensus exists regarding if opioids should 
be provided and if so, the dose, amount, and type to be given [10]. Additionally, a 
randomized controlled trial demonstrated that opioids did not improve pain with medical 
abortion but its results are limited, as it did not utilize an optimal dose or type of opioid [11]. 
Although further research is ongoing (Colwill, Fellowship Project) on the evaluation of 
opioid use for medical abortion related pain, opioids are increasingly under scrutiny due to 
the current U.S. opioid crisis and further restrictions may be put into place which may limit 
their use. 
 
The use of medical cannabis is increasing, most commonly for pain, anxiety and 
depression [12]. Currently, 28 states and the District of Columbia enforce legalized medical 
cannabis laws, and 8 of these states have also legalized cannabis for recreational use [13]. 
A 2015 national survey showed cannabis use is increasing, with past-month use increasing 
from 5.8% in 2007 to 8.4% in 2014 [2]. A 2016 survey of 226 women found that 19% self-
medicated with marijuana for pain during medical abortion, and all of these women reported 
some relief in pain [14]. 
 
Traditionally, ibuprofen are the mainstay of analgesia for abortion pain, with opioids 
commonly prescribed as an adjunct for pain control. Opioid pain medication use presents 
serious risks, including opioid-induced respiratory depression, overdose and opioid use 
disorder [15]. From 1999 to 2014, more than 165,000 people died from overdose related to 
opioid pain medication in the United States [16]. Even brief exposure to opioids can 
increase long term use. One study evaluated opioid-naïve patients who had undergone 
low-risk surgery, such as cataract surgery, and found that use of opioids within 7 days of 
surgery was associated with increased risk for use at 1 year [17]. A recent prospective 
study suggests that access to medical cannabis may decrease opioid use [18], thereby 
providing a safer alternative to opioid analgesia for some patients [19]. 
 
Marijuana is the common name for the Cannabis plant, from which at least 500 different 
compounds have been derived, including delta9-tetrahydrocannabinol (THC) and 
cannabidiol (CBD) [20]. The endocannabinoid system modulates neuronal and immune cell 
function, both crucial elements in the complex mechanism of pain perception, through two 
G protein-coupled cannabinoid receptors, CB1 and CB2. CB1 receptors are found primarily 
in central and peripheral neurons, whereas CB2 receptors are primarily expressed in 
immune cells [21]. Several studies have demonstrated the efficacy of cannabinoids in 
decreasing pain in chronic pain states such as multiple sclerosis and diabetic neuropathy 
[22]. However, less evidence exists for cannabinoids for treatment of acute pain. 
 
Delta9-tetrahydrocannabinol (THC) is a partial CB1 receptor agonist responsible for 
producing psychotropic effects. Delta9-tetrahydrocannabinol (THC) has been shown to 
reduce subject stress and anxiety [23]. Cannabidiol (CBD) is a non-euphoriant, anti-
inflammatory analgesic with CB1 and CB2 receptor antagonist and endocannabinoid 
modulating effects [24] [25]. As combining CBD with THC has been shown to reduce the 
psychotropic effects while maintaining the analgesic and anxiolytic effects of THC, there 


 
 
 
 
 
has been an emerging interest in blended cannabinoid products for various pain states [26]. 
A standardized, fixed 1:1 THC-CBD oromucosal spray has been approved to treated 
muscle spasticity in multiple sclerosis patients in 16 countries outside of the United States 
since 2012 and is currently in phase III trials within the United States [27]. At this time no 
FDA approved combined THC-CBD products exist, and significant regulatory hurdles 
prevent effective research on combined THC-CBD products.   
 
In the United States, synthetic delta9-tetrahydrocannabinol (THC) is available as Marinol 
(the generic is dronabinol) as an oral medication. This drug is approved by the FDA for two 
indications: chemotherapy-induced nausea and vomiting, and anorexia associated with 
weight loss in patients with AIDS. However, a number of studies has evaluated Marinol for 
chronic pain control, with mixed results [28]. The quality of evidence for pain relief in these 
studies were limited by the exclusion of participants with a history of substance abuse and 
other significant comorbidities, together with their small sample sizes. A small 2013 
randomized control trial showed the Marinol reduced pain in the acute setting, with the 
effect being comparable to smoked marijuana, but showed a longer lasting effect on pain 
control [29] [30]. 
 
Combining the anxiolytic and anti-emetic effects of THC with the analgesic effects of 
ibuprofen  is ideal for women undergoing abortion, as multiples studies have shown that 
women often report at least moderate levels of pain despite analgesia, and women who 
reports higher levels of anxiety experience significantly higher pain levels during abortion 
procedures [31] [32]. 
 
This study will be a randomized, double-blind, placebo controlled trial comparing pain levels 
in women undergoing medical abortion with one of two regimens: 1) ibuprofen 800mg and 
Marinol 5mg , and 2) ibuprofen 800mg and placebo pill at the time of misoprostol 
administration. Our primary objective will be to determine if a cannabinoid analgesic in 
addition to ibuprofen decreases maximum pain scores compared to ibuprofen and placebo 
when undergoing medical abortion. We plan to prospectively collect data via a text 
messaging system to evaluate pain scores, satisfaction, total analgesia use and adverse 
side effects. Results of this study will inform future providers who are counseling women 
undergoing medical abortion. 
 
4. Study Design 
This is a randomized, double-blind, placebo-controlled trial of women undergoing medical 
abortion through 10 0/7 weeks to compare maximum pain scores in women receiving a 
cannabinoid analgesic and ibuprofen 800mg versus placebo and ibuprofen 800mg ingested 
30 minutes prior to misoprostol administration. This study will be conducted at Planned 
Parenthood Columbia Willamette (PPCW) in Oregon. Potential participants will be 
approached by study staff after they have been fully consented for a medical abortion and 
been dispensed the abortion medications. Of note, the staff consenting subjects for the 
study will be different staff than those providing counseling about pregnancy options. Study 
procedures will be initiated following approval of the institutional review board at Oregon 
Health and Science University (OHSU), as well as approval from PPCW and Planned 
Parenthood Federation of America (PPFA). Study staff will thoroughly discuss the study 
with patients, assess for appropriate inclusion in the study, and consent the patients at the 
health center after completion of thorough counseling and consent for medical abortion.  


 
 
 
 
 
 
All patients desiring medication abortion at PPCW will receive standard of care 
independent of study protocol. Per PPCW normal clinical standards, after being consented 
for a medical abortion patients will receive mifepristone to take either in the clinic or at 
home, and misoprostol and ondansetron to take at home. PPCW staff will instruct patients 
when and how to take standard of care medications. For example, PPCW staff will instruct 
patients when and how to self-administer mifepristone and misoprostol. As standard of 
care, over-the-counter ibuprofen is recommended for pain management. Patients do not 
receive an ibuprofen package insert, and ibuprofen is not dispensed by PPCW. Narcotics 
are not routinely prescribed for pain control at PPCW. However, if patients call the clinic 
requesting additional pain medication, a provider may prescribe narcotic medication if 
appropriate.   
 
After consenting to medication abortion, OHSU study staff will approach PPCW patients 
about the study. Patients will be informed that they can participate in the study by their own 
free will, that their care will not change whether they choose to participate or not, and that 
they can be removed from the study at any time. If a patient desires study participation, 
informed consent will be obtained. The patient will then be randomized to either control or 
experimental arms of the study. The control arm receives 800mg ibuprofen and placebo 
and the experimental arm receives 800mg ibuprofen and 5mg Marinol. Because PPCW 
does not dispense ibuprofen, to standardize dose and timing, all patients will receive 
800mg ibuprofen as part of their study regimen. For this reason, ibuprofen is considered a 
study medication. All patients will take these study medications 30 minutes before 
misoprostol administration. Misoprostol administration will occur as directed to patient by 
PPCW staff. Randomization will occur at the OHSU Research Pharmacy per Research 
Pharmacy protocol. Placebo and study drugs will be similar in appearance. Subject and 
study staff will remain blinded to study drug allocation and study medications will be given 
out in a consecutive fashion. For example, study medications will be labelled as follows: 
Subject #5.  
 
After the patient enrolls, but at the time of the initial visit, study staff will initiate a test text 
message to ensure the participant has texting capabilities. TextIt Platform will be utilized to 
develop short messaging system (SMS) flow sheet scripts that will provide timed 
questionnaires to collect data. The patient will be given the study medications, including 
ibuprofen, and the study drug or placebo. The patient will be instructed to self-administer 
the ibuprofen, and study drug or placebo 30 minutes before PPCW instructed them to take 
their misoprostol medication. For example, if the patient was instructed by PPCW to self-
administer misoprostol at 11:30am, they would be instructed to self-administer the study 
drugs at 11:00am. 
 
Once the patient self-administers the misoprostol, the patient will trigger the text messaging 
script to begin and this will designate the start time of the study. Maximum pain scores 
using 11-point NRS (0-10) will be assessed at the time of misoprostol administration (“hour 
0”), at 6 hours after administration of misoprostol and at 24 hours. If a patient has not 
triggered the text messaging script within 24 hours following in office mifepristone 
administration, they will receive one text message and two phone calls to ensure they have 
not missed initiating data collection. Patients will be asked what time they intend to take 
misoprostol. If the patient has not triggered the text messaging script within 2 hours of the 


 
 
 
 
 
estimated time they reported they would be taking misoprostol, a text prompt will be sent 
reminding the patient to take misoprostol and report the time of self- administration. If a 
patient does not report the time of misoprostol administration within 48 hours of 
mifepristone administration, no additional pain scores will be collected. A satisfaction 
questionnaire will be completed via text message within 21 days of mifepristone 
administration. 
 
Thorough chart review at the follow up visit will collect and analyze unanticipated phone 
calls and/or clinical contact between the initial clinic visit and the follow-up visit. If a 
participant is found to have an ongoing pregnancy, further data will be excluded from the 
final analysis. Subjects will timestamp administration of additional pain medications within 
the first 24 hours after misoprostol administration via text message. If subjects would like to 
contact the study coordinators, they can text “Help” at any point via text message and be 
provided with a phone number to reach a study coordinator or study investigator.  
 
If a patient feels that their pain is not controlled with the prescribed study medications, they 
will be informed that they may call the advice line at the clinic or presents to clinic, and they 
may be prescribed additional pain medications at that time.  
 
Subjects will be compensated at three points in this study: 1) during initial enrollment in the 
study, 2) after responding to text message surveys for up to 24 hours after misoprostol 
administration, and 3) after completion of the follow-up visit or final text questionnaire. 
Compensation will be distributed in debit card (Clincard) form and tracked by serial number. 
Clincard is a web-based reloadable debit card used to reimburse patients who are engaged 
in clinical research. 
 
The primary outcome will evaluate the maximum pain score reported from the time of 
misoprostol administration to 24 hours after misoprostol administration. As less than 1% of 
women have ongoing pregnancies following the initial dose of misoprostol, we anticipate a 
very small number of women needing additional doses of misoprostol to complete their 
abortion and will not collect additional pain score data if additional misoprostol is 
administered [34]. If patients do not respond to text messaging at any point during data 
collection or do not complete a scheduled follow up appointment, we will attempt follow up 
with a maximum of one text and two phone calls. Study participation is considered 
complete following the follow-up visit survey or at 21 days following mifepristone 
administration. We will be following the SPIRIT guidelines for study design and the 
CONSORT guidelines for study reporting [35] [36]. 
 
Drug Dosing Guidelines for Pain 
Initial dosing:  
• Placebo Arm: Subjects will take ibuprofen 800mg and placebo 30 minutes prior to 
misoprostol administration.  
• Study drug (Marinol) Arm: Subjects will take ibuprofen 800mg and one (1) 5mg pill of the 
study drug 30 minutes prior to misoprostol administration.  
 
Re-dosing: Subjects will be able to re-dose ibuprofen 800mg every 8 hours as needed. If a 
patient calls the advice line or presents for an unscheduled encounter and requires 
additional medications, additional medication advice with be given.   


 
 
 
 
 
 
Study drug information and dispensing policies/security (see sections 6. Procedures 
Involved and 13. Drugs) for more information. 
 
Delta9-tetrahydrocannabinol (THC) is a partial CB1 receptor agonist, and is the component 
of cannabis best known for producing psychotropic effects. THC has analgesic, anxiolytic 
and anti-emetic effects. Marinol is a FDA approved synthetic form of THC which is why this 
drug was chosen for this study. Marinol is FDA approved to treat nausea in chemotherapy 
patients and poor appetite in AIDS patients. We will be using Marinol off-label to study the 
effects of THC on pain, anxiety and nausea during medical abortion.   
 
The time of onset is approximately 30-60 minutes, with peak effect at 90 minutes, and a 
half-life of 240 minutes, with a terminal half-life of 25-36 hours. 
 
In multiple reviews, Marinol is noted to have a favorable safety profile, with the most 
common side effects noted to be drowsiness, diarrhea and changes in appetite [37] [38]. 
There are no known fatalities from marijuana overdose in the United States [39].  
 
Marinol is FDA approved for oral administration and is available in 2.5mg, 5mg and 10mg 
pills. Marinol will be studied for off label use in this protocol, and the study dosage was 
selected based on expert opinion after surveying medical professionals familiar with 
medicinal THC use. 
Our proposed research use of Marinol meets criteria for exemption for an IND according to 
FDA guidance as: 
1) The drug product, Marinol, is lawfully marketed in the United States. 
2) Our investigation is not intended to be reported to FDA as a well-controlled study in 
support of a new indication and there is no intent to use it to support any other 
significant change in the labeling of the drug. 
3) Our investigation is not intended to support a significant change in the advertising or 
use of Marinol. 
4) Our investigation does not involve a route of administration, dose, patient population, 
or other factor that significantly increases the risk (or decreases the acceptability of 
the risk) associated with the use of the drug product (21 CFR 312.2(b)(1)(iii)).  We 
have selected a 5 mg dose for this single treatment, the mid-range of the approved 
pills and will give this by the approved oral route. 
5) Our investigation will be conducted in compliance with the requirements for review 
by an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR 
part 50). 
Our investigation will be conducted in compliance with the requirements of § 312.7 (i.e., the 
investigation is not intended to promote or commercialize the drug product). 
 
The placebo pill will be produced by the Oregon Health & Science University Research 
Pharmacy, and will be color and size matched.  
 
5. Study Population 
A. Number of Subjects 
Recruitment will mainly be focused at PPCW Southeast Health Center in Oregon. As an 
estimation, 680 medical abortions were performed within the last calendar year at the 


 
 
 
 
 
Planned Parenthood Beaverton clinic, which averages to 56 medical abortions per month. If 
recruitment is slower than anticipated, additional PPCW sites might be used. 
 
After written consent has been obtained and text messaging capabilities have been 
confirmed, participants will be randomized in a 1:1 allocation to the study drug and placebo 
groups. Randomization and drug packaging will occur at the OHSU Research Pharmacy per 
Research Pharmacy protocol. Placebo and study drugs will be similar in appearance. Subject 
and study staff will remain blinded to study drug allocation and study medications will be 
given out in a consecutive fashion. For example, study medications will be labelled as follows: 
Subject #5. 
 
We estimated our sample size to achieve 80% power to detect a 2 point reduction in the 
NRS for pain (standard deviation of 2.6 points) using a significance level of 0.05. 
Accounting for 20% participant withdrawal results in a minimum total sample of 
approximately 72 patients. We plan to enroll approximately 36 participants in each study 
arm.  
 
B. Inclusion and Exclusion Criteria 
Subjects will be approached about this study after the decision to proceed with medical 
abortion has occurred. Study staff will approach women at PPCW. Women will be informed 
that they can participate in the study by their own free will, that their care will not change 
whether they choose to participate or not, and that they can be removed from the study at 
any time without penalty.  
 
Subjects will receive detailed information regarding the study and an OHSU IRB approved 
consent form available in English will be reviewed and signed with interested participants. 
The patient’s medical chart will be reviewed and demographic and medical history will be 
collected to ensure eligibility. The study coordinator will send out a test text message to 
ensure the subject has text messaging capabilities. A recruitment log will track subjects who 
are excluded at any point throughout the study, or who decline entry. Their age, gestational 
age, and reason for exclusion or refusal will be documented.  
 
Subjects in this RCT will be recruited from women who have consented for an elective 
medical termination of pregnancy up to 10 0/7 weeks gestation dated by ultrasound at PPCW. 
 
Inclusion criteria:  
§ Aged 21 years or older 
§ Consented for elective medical abortion 
§ Pregnancy to 10 0/7 weeks, dated by ultrasound 
§ Able and willing to receive SMS messages via phone, and signed consent for e-
mail/text communications with OHSU healthcare providers 
§ English speaking 
§ Able and willing to give informed consent and agree to the study terms 
§ Have assistance at home; no motor vehicle use while taking study medications 
Exclusion criteria:  
§ Desires to continue pregnancy or currently breastfeeding 
§ Lack of access to cell phone and texting capabilities 


 
 
 
 
 
§ Prior participation in this study 
§ Early pregnancy failure 
§ Contraindications to the study medications: Marinol or marijuana derivatives, sesame 
oil, Ibuprofen 
§ Contraindications to medical abortion with Mifepristone or Misoprostol  
§ History of methadone, buprenorphine or heroin use within the last year 
§ History of a seizure disorder 
§ Used marijuana 5 or more days in the last week 
§ History of any adverse effects associated with prior use of recreational or medical 
marijuana products, or sensitivity/allergy to Marinol.  
Confidentiality of personal health information will be maintained according to HIPAA 
requirements for research. All subjects will receive a study number to which all subsequent 
data will refer. Personal identifiers will not be on questionnaires, data, abstract sheets, or in 
the main database. All data will be kept in locked files or a password protected computer.  
 
The data collected for subjects who are unable to be randomized in this study will be kept 
until study completion and all data has been analyzed. All study charts will remain on-site at 
PPCW until participant has completed study or until completion of study. At that point, study 
charts will be brought to OHSU. Study charts will be kept in a locked cabinet in a locked 
office when not being used by study staff.  
 
C. Vulnerable Populations 
Pregnant women are the subjects of this study. Planned Parenthood requires women to be 
capable of giving voluntary informed consent in order to receive abortion services. Subjects 
will need to be able to provide voluntary informed consent to participate in this study. This 
study will not target decisionally-impaired adults, non-English speaking patients or 
prisoners.  
 
D. Setting 
Recruitment, consenting, study procedures, and data analysis will occur by OHSU 
personnel at PPCW. Data analysis will also occur at OHSU. The OHSU Research 
Pharmancy will prepare the study drug and the placebo pills and will prepare the 
randomized medication packets for distribution in the clinic. We are relying on the OHSU 
Institutional Review Board (IRB) to satisfy IRB review requirements. 
 
Recruitment will occur at PPCW Southeast Health Center in Oregon. 680 medical abortions 
were performed within the 2016 calendar year at the Planned Parenthood Beaverton clinic, 
which averages to 56 medical abortions per month. If recruitment is slower than 
anticipated, additional PPCW sites might be used. Upon OHSU IRB approval, PPFA will 
review study prior to study initiation.  
 
E. Recruitment Methods 
When patient’s check in for their medical abortion appointment at PPCW, they will receive 
handouts (“Study Fact Sheet” and “Flyer”) informing them that they may be approached 
about a medical abortion study being conducted at PPCW through OHSU. 
 


 
 
 
 
 
Study staff will approach patients at PPCW after they have confirmed their desire to have a 
medical abortion. Women will undergo the standard assessment and care for medical 
abortion at PPCW. Patients interested in participating in this study will undergo screening to 
determine eligibility. Screening will be conducted in the form of chart review by study staff.  
Screening information will be kept in a de-identified screening log (# of people qualified or 
not qualified).  If eligible, interested participants will have time to review the consent form with 
study staff and have the opportunity to ask questions. The OHSU IRB approved consent will 
be signed by the participant and study staff.  
 
A recruitment log will track subjects who have signed consent and complete the study, as 
well as those who are excluded at any point throughout the study, or those who decline entry. 
Patient age, gestational age, and reason for exclusion or refusal will be documented. 
 
Subjects will be contacted via phone using SMS text messaging. 
 
Patients will be compensated up to $150 for participation in the study. Patients will be paid 
based on the number of study visits and text message responses completed, as outline 
below:   
• 
$10 after signing consent  
• 
$40 for completing all enrollment procedures (including randomization of study drug)  
• 
$50 for completing all text message surveys after taking Misoprostol ($15 per survey. 
$50 for completing all three surveys) 
• 
$50 for completion of follow-up appointment at PPCW or final follow up via text 
message survey  
 
F. Consent Process 
Study staff will approach patients at PPCW after they have confirmed their desire to have a 
medical abortion. Women will undergo the standard assessment and care for medical 
abortion at PPCW. Interested patients will undergo screening to determine eligibility in a 
private room at PPCW. Staff consenting subjects for the study will be different staff than 
those providing counseling about pregnancy options. If eligible, interested participants will 
have time to review the consent with study staff and have the opportunity to ask questions. 
The OHSU IRB approved consent will be signed by the participant and study staff.  
 
Ongoing consent will be reviewed on a monthly basis. In order to meet our 12 month 
recruitment goal, six (6) subjects must be enrolled monthly. PPCW Beaverton sees 56 
subjects per month on average for medical abortion. The principal investigator will staff a 
medical abortion clinic in order to maximize recruitment potential and decrease burden on 
the PPCW clinic. 
 
6. Procedures Involved 
Subjects will be approached after the decision to proceed with medical abortion has occurred. 
Study staff will approach women at PPCW. Women will be informed that they can participate in 
the study by their own free will, that their care will not change whether they choose to participate 
or not, and that they can be removed from the study at any time.  
 
Subjects will receive detailed information regarding the study and an OSHU IRB approved 
consent available in English will be signed with interested participants. The patient’s medical 


 
 
 
 
 
chart will be reviewed and demographic and medical history will be collected. The study 
coordinator will send out a test text message to ensure the subject has text messaging 
capabilities. A recruitment log will track subjects who are excluded at any point throughout the 
study, or who decline entry. Their age, gestational age, and reason for exclusion or refusal will 
be documented. Patients will not have access to other opioid prescription medications outside 
of the study. 
 
After written consent has been obtained and text messaging capabilities have been confirmed, 
participants will be randomized in a 1:1 allocation to the study drug and placebo groups. 
Randomization will occur at the OHSU Research Pharmacy per Research Pharmacy protocol. 
The study medication or placebo capsules will be placed in identical packets, labelled only with 
the study identification number and instructions for use so as to maintain blinding. Investigators 
will assign each participant a study identification number in sequential order as they enroll, and 
they will receive the study medication packet with that same identification number. 
 
Each study arm will include 36 subjects for a total of 72 subjects.  
 
At the time of randomization, subjects will be shown an 11-point Numeric Pain Rating Scale 
(NRS) handout (See Appendix A) and allow for any questions about responding to questions 
relating to reporting pain. Data will mainly be collected via SMS messaging using timed surveys 
at 6 and 24 hours. Final data will be completed via chart review after the scheduled follow-up 
visit or 21 days after mifepristone administration. 
 
If a participant does not respond to text messaging, we will attempt to contact the participant via 
text message twice, and call once. If a participant does not come to their follow up appointment, 
we will again attempt to contact by text message and phone call. If a participant receives care 
at another facility, we may request records from that facility for review. 
 
 
Subjects have the right to withdraw from the study at any time. Once a participant indicates their 
request for withdrawal, no further data will be collected. Participants will be provided with contact 
information and their reason for discontinuation will be recorded.   
 
No laboratory evaluations will be conducted for this research study. Women will receive a follow-
up ultrasound as standard of care to evaluate completion of the medical abortion per Planned 
Parenthood guidelines.  
 
Data management will be managed by the PI. Baseline data will be collected at the initial visit 
by the study coordinator and PI. All data being collected after administration of misoprostol and 
study medications will be collected and stored on a secure server. Data regarding completion of 
medical abortion will be followed up via chart checking the electronic medical record of Planned 
Parenthood (NextGen). 
 
All subject data will be kept confidential and locked in an office and on a password-protected 
computer. Each subject will be assigned a unique study identification number. A file linking 
subjects with their study ID and name will be kept in a locked file in the PI’s office and stored 
separately from the data files. Only the study investigators will have access to this file. No subject 
names will be included in the study data during statistical analysis. The study coordinator and 
PI’s telephones will be encrypted by OHSU and password protected. 


 
 
 
 
 
 
Periodically, data will be pulled from the server and entered into REDCap and STATA. Random 
data entry checks will be performed to verify accuracy. 
 
Delta9-tetrahydrocannabinol (THC) is a partial CB1 receptor agonist, and is the component of 
cannabis best known for producing psychotropic effects. We will be using Marinol, a synthetic 
form of THC, which is FDA approved for use for treating nausea in chemotherapy patients and 
low appetite in AIDS patients. 
 
The time on onset is approximately 30-60 minutes, with peak effect at 90 minutes, and a half-
life of 240 minutes. 
 
In multiple reviews, cannabinoids are noted to have a favorable safety profile, with the most 
common side effects noted to be feeling “high”, drowsiness, diarrhea and changes in appetite 
[37] [38]. There are no known fatalities from marijuana overdose in the United States [39].  
 
We will be using 5mg Marinol pills. The study drug dosage is based on expert opinion and 
market research, as there is a paucity of research on THC use in similar acute pain settings. In 
the absence of data to support a dose-effect for management of pain and anxiety for medical 
abortion, we selected 5 mg as an appropriate dose for initial study. We considered that 2.5 mg 
may be sufficient to improve appetite, but that most patients require dose escalation.  Since 
the typical approved use requires dosing prior to each meal, with total daily doses of 7.5 – 20 
mg, we feel our 5 mg dose represents an appropriate selection for an initial study.  
 
The placebo pill will be produced by the Oregon Health & Science University Research 
Pharmacy, and will be color and size matched.  
  
  
 
 
Marinol has the following structural formula: 
 
Dronabinol, the active ingredient in MARINOL (dronabinol capsules, USP), is synthetic delta-9-
tetrahydrocannabinol (THC). 
 


 
 
 
 
 
Manufactured by: Patheon 
Softgels Inc. 
High Point, NC 27265  
 
Manufactured for: AbbVie Inc.  
North Chicago, IL 60064  
 
Full prescribing information:  
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018651s025s026lbl.pdf 
 
Ibuprofen (Motrin) - Subjects will be taking 800mg tablets. Ibuprofen is a nonsteroidal anti-
inflammatory drug. Its mode of action is not completely understood, but may be related to 
prostaglandin synthetase inhibition. Ibuprofen is (+) -2- (p – isobutylphenyl) propionic acid. Its 
chemical structure is: 
 
 
Manufacturer: 
Major Pharmaceuticals 
17177 North Laurel Park Suite 233 
Livonia, MI 48152 
Full prescribing information: 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf 
 
7. Data and Specimens 
Handling of Data and Specimens 
 
Data management will be managed by study staff. Baseline data will be collected at the 
initial visit by the study staff. All data being collected after administration of misoprostol and 
study medications will be collected and stored on a secure server. Data regarding 
completion of medical abortion will be followed up via chart checking the electronic medical 
record of Planned Parenthood (NextGen). 
All subject data will be kept confidential and locked in an office and on a password-
protected computer. Each subject will be assigned a unique study identification 
number. A file linking subjects with their study ID and name will be kept on a secure 
OHSU server and stored separately from the data files. Only the study staff will have 
access to this file. No subject names will be included in the study data during 
statistical analysis. The study staff’s telephones will be encrypted by OHSU and 
password protected. Periodically, data will be pulled from the server and entered into 
REDCap and STATA. Random data entry checks will be performed to verify 
accuracy. 
Sharing of Results with Subjects 
Data results will not be shared with subjects or their providers. 
 


 
 
 
 
 
Data and Specimen Banking 
The data collected in this study will be stored per OHSU guidelines after completion of all 
data analysis and publication. Study data will not be used for further research. We are not 
collecting any specimens for this study. 
 
8. Data Analysis 
We will use descriptive statistics to characterize the sample and test for differences in 
baseline demographic and clinical characteristics between treatment groups using Student’s 
t-test, the Wilcoxon rank-sum test, Pearson’s chi-squared test, or Fisher’s exact test, as 
appropriate. 
 
For the primary and secondary outcomes, we will follow the intention-to-treat principle, 
including all participants who provide pain scores. Based on previous medical abortion pain 
studies [9], we assume that maximum pain scores will not be normally distributed, so we will 
use a Wilcoxon rank-sum test to compare maximum NRS pain scores between the control 
and experimental groups. We will test for differences in NRS between the overall treatment 
groups. For multivariable analysis of maximum pain scores, we will construct a proportional-
odds cumulative logit model, a rank-based linear model, or a linear model on transformed 
data, depending on distribution of the data and model fit, with treatment group as the main 
predictor and adjusted for baseline demographic and clinical variables.  
 
To make use of the repeated pain measures, we will use a generalized estimating equation 
(GEE) to model pain scores during the first 24 hours.  
 
We will use logistic regression models to examine differences between groups in the 
following outcomes (all models will have treatment group as the main predictor and will be 
adjusted for baseline demographic and clinical characteristics):  
• Proportion of women reporting a maximum pain score of 7 or higher 
• Use of rescue medication; this model will also adjust for the number of ibuprofen and 
Marinol or placebo doses taken 
• Presence of nausea or vomiting 
• Satisfaction with pain medication 
• Need for additional (non-prescribed) pain medication 
 
To examine differences between groups in the amount of ibuprofen and Marinol or placebo 
used during the 24 hours after administration of misoprostol, we will use Poisson, negative 
binomial, or zero-inflated Poisson or negative binomial regression models, depending on the 
distribution of the data. 
 
We will use descriptive statistics to characterize the number and chief complaints of patient-
initiated phone calls to the provider or clinic. We will use Student’s t-test or a Wilcoxon rank-
sum test to test for differences between groups in the number of calls placed. We will group 
chief complaints into broad categories and test for differences across treatment groups using 
a chi-squared test. Similarly, we will group non-prescribed medications used for pain into 
broad categories and use descriptive statistics to characterize them.  
 
Finally, we will use descriptive statistics to summarize adverse events.  
 


 
 
 
 
 
Previous studies suggest that the 11-point numeric pain scale are as sensitive to changes 
in clinical pain as the visual analog scale.18 We will administer numeric pain scales via text 
message that will prompt participants to rate their pain on a scale of 0-10. Significant 
difference in pain intensity for the numeric pain scale is a change in >2. [42] 
We will define a clinically significant change by a change in numeric pain of 2.  
 
The sample size calculation was based on a simulation study using a Wilcoxon rank sum test 
on data simulated from specified parameters (delta=2, sigma=2.6, alpha=0.05). It is difficult 
to simulate categorical data unless we assume a specific probability for each possible value 
of the NRS, which would be far too strong of a set of assumptions to make. For this reason, 
we treated the outcome as continuous and used a standard deviation as a measure of spread 
for the purpose of simulating data, and then used the more conservative rank-based test to 
calculate the sample. To calculate sample size, we simulated pools of test and placebo 
ordinal NRS data whose means were 2 units apart and whose spreads were both 2.6 
standard deviations. We selected these continuous and symmetric measures of center and 
spread in the absence of the availability of any other distributional assumptions of NRS data. 
The simulated pools of data were constrained to integer values ranging from 0 to 10. We 
repeatedly sampled from the simulated pools of data at sample sizes ranging from 10 to 100 
per cell to calculate the probability of a significant (at alpha=0.05) Wilcoxon rank-sum test at 
each sample size. A sample size of 28 participants per group provided 80% probability of 
detecting the 2-point difference in the simulated data. To allow for up to 20% drop-out, we 
propose to enroll 36 participants per study arm (a total of 72 participants). 
 
9. Privacy, Confidentiality, and Data Security 
Data collection and storage: Standard institutional practices will be followed as described 
in the OHSU Information Security and Research Data Resource Guide 
(http://ozone.ohsu.edu/cc/sec/isg/res_sec.pdf) to maintain the confidentiality and security of 
data collected in this study. Study staff will be trained with regard to these procedures. 
Paper files will be stored in locked filing cabinets in restricted access offices at PPCW and 
OHSU. Electronic data will be stored in the secure web-based data collection system, 
REDCap, and TextIt which is housed on an OHSU secure server. Access to data is 
restricted to study personnel.  
Data coding: Upon enrollment, subjects will be assigned a code that will be used instead 
of their name, medical record number or other personally identifying information. Electronic 
files for data analysis will contain only the subject code. Codes will not contain any part of 
the 18 HIPAA identifiers (initials, DOB, MRN). The key associating the codes and the 
subjects’ personally identifying information will be restricted to the PI and study staff. The 
key will be kept secure on a restricted OHSU network drive a in a limited access folder.  
Final disposition of the data: The data collected in this study will be stored per FDA 
guidelines after completion of all data analysis and publication. Study data will not be used 
for further research. We are not collecting any specimens for this study. 
 
Texting with Subjects: Information Privacy Security review was conducted and approval 
provided per email correspondence on 5/July/2018 contingent on having a signed BAA in 
place.  Upon further review, the legal and security review team determined that due to the 
limited way that PHI is shared on this platform, neither a security review nor BAA are 
considered necessary.  This is documented via email communication on 


 
 
 
 
 
5/September/2018.  When OHSU implements an enterprise security texting application the 
Women’s Health Research Unit will agree to switch to using this for study data collection 
and communication with study subjects for all studies moving forward.  
 
10. Provisions to Monitor the Data to Ensure the Safety of Subjects 
Please see Data Safety Monitoring Plan (DSMP).  
 
11. Risks and Benefits 
 
Risks to Subjects 
A foreseeable risk to participants participating in this research would be a breach of 
confidentiality. Patients will be counseled on this risk and encouraged to take steps to 
protect confidentiality by password protecting their cell phone and keeping it on their person 
for the duration of the study. The list of questions that will be sent over text will be provided 
for review and patients will be asked to sign an additional consent to receive the questions 
via text message. There are no anticipated inconveniences to study subjects related to 
participation in the research, as no additional procedures, tests or interventions will be 
performed apart from routine medical services provided to women seeking abortion care at 
Planned Parenthood. 
 
Another risk to taking part in this study is that the study drug or the dose a participant 
receive may not be effective in helping to treat their pain. This means subjects may spend 
time in the study and experience side effects taking a drug that may not provide subjects 
with any health-related benefits. If a subject is not in the study, their treatment for pain 
during medical abortion would be determined by PPCW which could include ibuprofen. By 
participating in the study, the only additional risk would be exposure to cannabis if a subject 
is in the study drug group. 
 
As cannabis can be testing in urine drug screens, used by some employers, patients will be 
counseled before enrollment that if they receive the study drug, this may result in a positive 
drug test. They will be counseled that employers still reserve the right to terminate 
employment or enact other forms of discipline based on a positive urine drug screen 
despite the fact that cannabis is legal for medical and recreational purposes in the state of 
Oregon. If they choose to participate in the study, the study team is not responsible for any 
legal consequences of a positive urine drug screen. 
 
If a participant is nursing an infant or planning to continue a pregnancy, then a participant is 
not eligible for the study. In the rare possibility that a medical abortion fails and a subject 
has an ongoing pregnancy and decides to keep the pregnancy, then the use of cannabis 
products is category C. This means that animal studies have shown an adverse effect on 
the fetus and there are no adequate and well-controlled studies in humans, but potential 
benefits may warrant use of the drug in pregnant women despite potential risks. The use of 
ibuprofen in the first trimester of pregnancy are category B. This means that the medication 
is generally safe to use during the first trimester of pregnancy, and the risks to the 
developing fetus are low. Patients will be counseled that risk of cannabis products to a 
developing fetus or a breastfeeding infant is not known, and as a result, the American 
Congress of Obstetrics and Gynecology recommend not using cannabis during pregnancy 
or while breastfeeding.  


 
 
 
 
 
 
B. Potential Benefits to Subjects 
Subjects may or may not personally benefit from being in this study. However, subjects will 
help us learn how to benefit patients in the future. 
 
12. Resources Available  
Subjects will have access via phone to a Family Planning trained Obstetrics and 
Gynecology specialist available during the length of the study for any questions or 
concerns. Subjects will be given the contact number for the Women’s Health Research Unit 
(WHRU) and the OHSU Paging Operator to ask to have on-call provider paged.  
 
13. Drugs  
Marinol, the study drug, is FDA approved in the United States for the treatment of nausea 
in chemotherapy patients and low appetite in AIDS patients. However, it has not been 
studied to treat pain or nausea during medical abortion. We have included the Marinol 
Summary of Product Characteristics (Appendix B), which provides safety and 
pharmacokinetics information.. 
 
The study drug dosage is based on expert opinion and market research, as there is a 
paucity of research on THC use in similar acute pain settings. Medical professionals 
familiar with Marinol and medical marijuana, cannabis product producers and dispensary 
staff were surveyed on the most appropriate dosage for a marijuana naïve patient seeking 
relief from strong, acute cramping abdominal pain.  
 
Marinol is a schedule III drug, and the OHSU Research Pharmacy will store the study drug. 
Packing of the study medications will also be handled by the OHSU Research Pharmacy 
for adequate blinding.  
Subjects will return any unused medications at the end of study participation. 
 
14. Multi-Site Coordination  
Planned Parenthood Federation of America (PPFA) will have the most current version of 
the protocol, consent and HIPAA authorization. PPFA will independently review the study. 
A research service agreement will be signed by OHSU and PPFA. All engaged participating 
sites will safeguard data as required by local information security policies. All local site 
investigators will conduct the study appropriately. All non-compliance with the study 
protocol will be reported in accordance with local policy. Communication of problems will be 
managed by the study PI. Interim results and study closure will be handled by the study PI. 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
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Appendix A 
 
 
 
 
  0–10 Numeric Pain Rating Scale 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
Moderate 
Worst 
pain 
pain 
possible 
pain 
 
 
 
 
 
 
 
 
 
 
Appendix B Marinol Package Insert (see attachment)