Arnica and the Management of Pain in Acute Musculoskeletal Extremity Injuries
Phase: PHASE2
Conditions: Pain, Muscle, Pain, Acute
Sponsor: Children's Hospitals and Clinics of Minnesota

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Arnica and the Management of Pain in Acute Musculoskeletal 
Extremity Injuries 
 
 
 
Principal Investigator: 
Manu Madhok, MD, MPH 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Coordinator: 
Shea Lammers, MS 

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1.  Study Team  
Principal Investigator: Manu Madhok, MD, MPH 
Study Coordinator: Shea Lammers, MS 
 
2.  Project Title 
Arnica and the Management of Pain in Acute Musculoskeletal Extremity Injuries 
 
3.  Introduction 
Background/Significance 
The Emergency Department (ED) at Children’s Minnesota is a Trauma 1 Center which takes care of 
our state’s most severely injured children. However, the majority of traumas it sees are not severely 
injured but patients with minor to moderate injuries. These patients enter the ED scared and in pain 
with concerned parents. Our institution’s “Children’s Comfort Promise” initiative advocates 
effectively using institutional guidelines and evidence-based research to control the pain all our 
patients feel during and following their visit.  
 
Pain management in Emergency Department is a key marker for quality of care and the focus is on 
providing it in a safe, effective and timely manner (Guidelines by Emergency Medical Services, 
online access). However, there is no standard of care for the management of acute musculoskeletal 
injury in children (Ali 2010). Currently, ibuprofen is a favorable choice for the treatment of acute 
musculoskeletal injury pain. Yet studies have shown concern for delayed healing activity associated 
with NSAIDs like Ibuprofen (Boursinos 2009). 
 
In current practice, we do not offer alternative medications. Homeopathic Arnica Montana is a well-
established complimentary medicine and may provide a good alternative for managing acute pain 
from musculoskeletal injuries, especially in children, given the palatability and rarity of side effects. 
Extracted from the herb native to the Swiss Alps and the Rocky Mountains, it is commonly used as 
a topical treatment or an ingestible tablet, but is also found in many mainstream foods, shampoos, 
and cosmetics (Kouzi 2007).   
 
In adult patients, homeopathic Arnica has been used and studied for it analgesic and anti-
inflammatory effects in many surgical settings with mixed results. Placebo-controlled, randomized, 
double-blinded studies trying to control post-procedural ecchymosis (Kotlus 2010) and pain (Paris 
2008) have shown no efficacy of Arnica treatments. Another study focusing on face-lift surgery 
showed a statistically significant improvement in post-procedural bruising, but did not demonstrate 
any improvement in how the patient felt post-operatively (Seeley 2006). Some studies, such as a 
study conducted on 190 patients who underwent a tonsillectomy, have shown statistically 
significant decreases in post-operative pain scores (Robertson 2007) as a result of Arnica treatments.  
Another study which looked at swelling after knee surgery showed a statistically significant 
decrease in knee circumference after taking Arnica post-operatively as compared with placebo 
(Brinkhaus 2006). Most of the studies were done in adults patients. The effect of Arnica in children 
with acute musculoskeletal injury is not well studied and needs to be addressed.  
 

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Research Question 
To compare usual care vs. usual care plus Arnica 1M* (oral) or the placebo for management of pain 
in acute musculoskeletal extremity injuries. The primary outcome is to determine if subjects use less 
ibuprofen when given Arnica 1M. 
 
Secondary objective:  
To determine if Arnica 1M provides better improvement of pain score  
To determine if Arnica 1M provides better relief of swelling  
 
*The concentration of Arnica in a 1M potency remedy is 1 part Arnica in 101000 parts water (Kayne 
2006). 
 
4.  Study Design and Methodology 
Hypothesis 
Subjects use less ibuprofen when given Arnica 1M (oral) plus usual care than given placebo plus 
usual care.  
 
Overview/Scope 
Study Design 
This is a randomized, double-blind, placebo-controlled clinical trial.  
 
Time Frame/Duration 
 During the month following IRB approval, the study team will begin training research assistants 
on the study procedures. The PI will attend ED nursing huddles and physician and nurse 
practitioner staff meetings to introduce the study, describe the procedures each groups is 
expected to complete, and answer questions.  
 Once training is complete, enrollment will begin. Active enrollment will take place in the Saint 
Paul and Minneapolis ED. We anticipate enrollment to take two years.  
 Following enrollment, the data will be analyzed and prepared for publication over four months.  
 
Analysis 
Sample Size 
A sample of 324 patients (162 assign to the arnica plus usual care group and 162 assigned to the 
placebo plus usual care group) has 80% power to detect a 1 dose reduction of ibuprofen in the 
arnica group compared to the placebo group using a two sample t-test at the 5% significance level. 
 
The power calculation assumes a clinically relevant reduction of 20% total ibuprofen dosage and 
published literature on ibuprofen use in pediatric patients following an arm fracture. Drendel et al 
(2009) showed that patients took 5 doses of ibuprofen on average with a standard deviation of 3.2 
doses in the first 72 hours after discharge from the emergency department. A 20% reduction 
corresponds to a reduction of 1 dose on average. 
 
Analytic Approach 
A linear mixed model with the dose reduction of ibuprofen as the dependent variable and, time of 
Arnica/placebo taken, time of ibuprofen taken and dosage, and Arnica 1M (oral) or placebo group 
as the predictors will be used to analyze the data to determine if Arnica 1M (oral) provides better 

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pain relief than placebo in conjunction with standard of care medications. Since participants will be 
repeatedly measured repeated effect will be used to model the possible correlation of the residual 
errors within each participant.  
 
A two-sided p-value < 0.05 will be used for significance. All analysis will be completed using SPSS 
V23.0 (SPSS Inc., Chicago, IL). 
 
5.  Subjects 
Subjects 
162 Subjects in each group, control and experimental, will be required to complete the protocol 
through follow-up.  At least 324 total subjects will be enrolled and randomized in this study. 
 
Recruitment 
1. A trained research assistant will identify patients with extremity injuries and approach the 
treating physician to check eligibility criteria.  
2. The research assistant will approach each patient meeting the inclusion criteria. Study goals and 
objectives will be shared with the patient and parents. Study concepts that are often difficult to 
understand, such as randomization and blinding, follow-up and data collection, will be 
explained to the participants and the research staff will allot time for questions.  
3. After this process, consent, assent, and HIPAA authorization will be obtained. Patient and 
parent will be educated on assessment of pain, record medication daily diary and use 
homeopathic medication. (Appendix 1. Parent Take Home Table, Appendix 2. Instructions for 
use of homeopathic remedies, Appendix 3. What is Homeopathy) 
4. The treating physician will be informed and will place orders for the study medication. The first 
dose of study medication or placebo will be administered at ED (Appendix4. Parent Handout). 
The ED physician/nurse practitioner will discharge patients with current standard instructions 
for soft tissue injuries.  
5. A $10 reimbursement of either a Target gift card that will be mailed or a Clincard will be loaded 
at the completion of the study to compensate for their time in providing needed data during 
telephone follow-up. 
 
Enrollment 
Inclusion Criteria 
 Patient’s age is between 11 years and 18 years 
 Patient presents to the Department with an acute, soft tissue ankle or forearm injury  
 Patient has noticeable swelling or bruising at the site of injury 
 Patient’s initial recorded pain score of 4 or higher on a pain scale of 1 to 10 
 Patient’s and family’s willingness to participate in telephone follow-up 
 
Exclusion Criteria 
 Patient is diagnosed with a fracture, either in the ED or upon review by radiology. 
 Patient has an allergy to ibuprofen 
 Patient is already on a NSAID, acetaminophen, anticoagulant or oral corticosteroid therapy for 
chronic pain treatment (a NSAID given in triage or use for the current injury is allowed). 
 Use of other concurrent complementary medicine therapy, e.g. massage, acupuncture, physical 
therapy 

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 Patient has been treated for this injury in the past 
 Patient has a bleeding/bruising disorder 
 Patient is pregnant or is lactating. 
 Patient has a liver or kidney disease, malignancy, infection, immunodeficiency or metabolic 
syndrome 
 Patient is allergic to the Asteraceae family of plants (arnica, ragweed, chrysanthemum, 
marigold, or daisy are the most common) 
 Patient is nonverbal, and thus unable to give a pain score 
 Patient does not have a working telephone 
 Family requires foreign language interpreter during their ED visit. 
 
6.  Study Procedures 
 
The graphic to the left details the step-wise flow of the 
study from enrollment to completion for each patient.  
 
1. During the ED visit 
The Emergency Department provider will provide 
standard of care treatment. The potential patients will 
be identified and approached. Consent, assent, and 
HIPAA authorization will be obtained.   
 
After consenting, the patient will be randomized to 
Arnica or Placebo in conjunction with standard 
treatment of ibuprofen. Randomization will be 
conducted by the inpatient pharmacy in a fashion 
which ensures both the investigators and subjects are 
blinded to the intervention group.  
 
The study drug will either be the Arnica 1M (oral) or 
placebo. The Arnica 1M oral pill will be a sucrose 
sugar pill, which is medicated with the Arnica 1M 
liquid. The placebo used will be an un-medicated sugar 
pill. Each dose is two pills. 
 
The Arnica 1M solution will be purchased through 
Helios Homeopathy Ltd., which is based in the United 
Kingdom, and will be received, stored, and distributed 
by the Children’s Inpatient Pharmacy. Doses will 
arrive in bulk, and be separated into vials with 10 pills (i.e., 4 doses and 1 extra dose in case pills 
are accidently dropped while dispensing from the vial). 
 
The study drug will be ordered by the attending ED provider. Pharmacy will use a pre-determined 
randomization table to randomize and fill the order. They will send the vial containing the study 
medication. The ED research assistant will pick up the study drug vial and counsel the family, then 
will guide and observe the self-administration of the first dose of medication. 

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The patient’s pain score at the time of study enrollment will be collected from the patient, and 
highest pain score during the ED visit will be collected from the EMR. After the pain score is 
assessed in the ED, the RA will measure and record the width of both the uninjured and the bruised 
joint (ankle or wrist) using a paper measuring tape that is used in ED. Simultaneously, the RA will 
show the parent/guardian how to measure the injured joint.  
 
2. After discharge, follow-up call 
Each subject will be given a study sheet (Appendix 1) on which they can record their pain score 
once per day in the morning after wake up for 3 days which will include a VAS. It will help track 
how many doses of Arnica the patient took, as well as how many doses of ibuprofen the patient 
took. It will allow the family to track if the joint was iced or immobilized. This information will be 
collected during the follow-up phone call. 
 
At home, on day 1, 2, and 3, the parent/guardian will repeat the measurement on the injured joint 
and record the value on the study sheet. This data will be collected during the follow-up call. 
 
In addition to the data mentioned above, the study team will ask the parent/guardian if the subject 
has had any loss of function due to the injury, had returned to full activity following the injury, had 
any missed school or summer activities, if the parent/guardian missed work due to the injury, or if 
the family returned to the ED or to another medical facility due to the injury. The RA will ask the 
parent if the patient experienced any side effects, specifically rash, abdominal pain, nausea, 
vomiting, or fatigue and will ask if they experienced any other effect.   
 
Parent that signs the consent will be the only one designated to track all info required. 
 
Data Requirements 
 
1. Following consent, MRN, date of visit, patient’s full name, parent/guardian’s first and last 
name, mailing address, phone number will be collected from the parent. 
2. Demographic information including patient’s race, ethnicity, date of birth and gender will be 
collected from the medical record.   
3. During ED visit and the follow-up calls, all research questions will be answered by 
parent/guardian. Data elements include:  
 
 Site of injury 
 Pain score 
 Swelling measurement in ED 
 If bruising was present at onset, how it has changed over day 1, 2 and 3. 
 If splint applied 
 If ice applied during ED visit 
 Medication prescribed by ED provider 
 If the patient take all 4 doses of the study medication 
 Pain score in day 1, 2 and 3 
 If the patient takes ibuprofen, and dose in day 1, 2 and 3 
 If the patient seeks health care since the ED visit 

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 How many days of school and/or activities the patient missed  
 How many days of school, work the family members missed 
 How many days has the family’s usual routine been changed or disrupted 
 If the patients experienced: rash, abdominal pain, nausea, vomiting, fatigue 
 If topical treatments were used, and what kind 
 
Data will be acquired from the patient and family member/ guardian as well as the treating provider 
and the electronic medical record (EMR). Appendix 5 describes the data elements captured for this 
study.  
 
Data will reside in a customized REDCap database residing on the Children’s secure network 
(Appendix 5). Data obtained from the medical record will be immediately added to the secure 
database. All data from the patient and family, both in the ED and during the telephone follow-up 
call, will be recorded on a paper data collection sheet and then transferred into the REDCap 
database. 
 
Visit Schedule 
1. During the ED visit 
The potential patients will be identified and approached. Consent, assent, and HIPAA authorization 
will be obtained. 
 
Other research relevant info will be collected during patients’ visit in ED. Patients will be trained in 
using the study sheet (Appendix 1), and measuring swelling.  
 
2. After discharge, follow-up call 
One follow-up call will be made during day 4-6 after discharge. The information that patient 
recorded on study sheet will be collected during the follow-up phone call.  
 
Drug/Device, Handing, Storage (If Applicable) 
Homeopathic remedies are prepared by serial dilution and succussion of a “mother tincture”. The 
mother tincture is composed of the herbal material, in this case Arnica Montana, and water or 
alcohol (Kayne, 2006).   
 
To prepare a 1M Arnica remedy, one drop of the Arnica mother tincture is added to 99 drops of 
highly purified water in a clean glass vial.  The vial is vigorously shaken while striking the vial on a 
hard surface. This shaking process is known as succussion (Kayne, 2006).  The resulting mixture 
has a potency of 1c. The 1c solution is then emptied from the vial, leaving residual droplets.  99 
drops of water are then added to the vial and again succussed to produce a mixture potency of 2c.  
Each time the solution is diluted and succussed the potency of the mixture increases while the 
concentration of Arnica decreases. This process is repeated 1000 times to reach a potency of 1000c 
or 1M. The concentration of Arnica in a 1M potency remedy is 1 part Arnica in 102000 parts water 
(Kayne, 2006). Several hypotheses have been put forward to explain the potentisation phenomenon 
cause by succussion, but homeopaths agree that the process of dilution and succussion preserve the 
therapeutic effect of the original substance while removing the negative side effects, making each 
homeopathic treatment, ideally, safe and effective (Bellavite 2002, Kayne, 2006). 
 

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For patients in the Arnica group, this remedy is loaded onto the sucrose pellets by placing 1-3 drops 
of Arnica 1M in each vial and shaking the vial to coat the pellets. Each four dose vial will contain 8 
sucrose pellets, and an additional 2 pellets in case some are dropped. 
 
Each patient will take the first dose in the ED and take additional doses of the provided medication 
(Arnica or placebo) every 4 waking hours. After 24 hours, any untaken doses should be discarded. 
If additional pain control is needed, patients should take ibuprofen as needed.  
 
Topical Arnica remedies, which could be applied directly to the injury site, were an alternative 
treatment option. The study team elected to use oral medications as the previous studies which 
showed efficacy used Arnica taken orally (Seeley 2006, Robertson 2007, Brinkhaus 2006). 
 
Patient Withdrawal, Completion, Death 
In the case of adverse events requiring medical attention, the subject and family will be un-blinded.  
If the subject is un-blinded prior to completing the study, they will be withdrawn from the study. 
 
If the subject needs to be un-blinded for any reason, authorization may be given by PI Dr. Manu 
Madhok. Authorization may be written or verbal. The unblinding procedure is in risks/benefits 
section. 
 
Patients who have any of the contraindicated conditions listed in the Risks section will be excluded 
from the study. 
 
7.  Risks/Benefits 
 
Potential Risks 
Arnica usage is contraindicated in patients who have an allergy to the Asteraceae family of plants as 
well as in patients who are pregnant or lactating, who have an existing liver or kidney disease, 
bleeding or bruising disorder, malignancy, infection, immunodeficiency or metabolic syndrome.   
 
Arnica should not be used in conjunction with any other homeopathic remedies or treatments.  
Ingestion of large doses of herbal preparations of Arnica Montana may lead to gastroenteritis or 
internal bleeding (Kouzi, 2007) although none of the randomized, placebo controlled studies 
reported a single instance either of these complications (Brinkhaus 2006, Seeley 2006, Robertson 
2007, Paris 2008, Kotlus 2010) likely due to low doses of the extracted tincture.  
 
Because data will be collected from patient records, there is a risk for breach of confidentiality.  
 
Methods to Minimize Risks 
Our study uses low dose Arnica 1M which is a 1 part sesquiterpene lactone, the active compound in 
Arnica, in 101000 parts solution. This dosage is lower than the dosages used in all the studies 
referenced in the background (Brinkhaus 2006, Seeley 2006, Robertson 2007, Paris 2008, Kotlus 
2010) and fewer doses will be delivered than in these previous studies. Patients with new symptoms 
which may indicate gastroenteritis or internal bleeding will be instructed to return to the Emergency 
Department for treatment. 
 

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In the case of adverse events requiring medical attention, the subject and family will be un-blinded.  
If the subject is un-blinded prior to completing the study, they will be withdrawn from the study. 
 
Patients who have any of the contraindicated conditions listed in the Risks section will be excluded 
from the study. 
 
Potential Benefits 
Patients receiving Arnica 1M (oral) may experience reduced pain, swelling and/or bruising during 
the course of their treatment in the study. 
 
The results of this study may provide ED providers with data showing the benefits of a homeopathic 
treatment for pain, bruising, and swelling to be used in addition to standard of care medication or by 
itself. 
 
Adverse Events 
There are no anticipated adverse events of our study. 
 
Patients experiencing new symptoms due to ingestion of the treatment will be recommended to 
cease taking the Arnica 1M pills or the placebo. The subject will be withdrawn and un-blinded from 
the study. The PI will be contacted and may recommend a return to the ED for further work up and 
treatment. Unanticipated adverse events will be reported to the Institutional Review Board at 
Children’s Hospital as required by the Code of Federal Regulations. 
 
A Data Safety Monitoring Board (DSMB) has been established internally at Children’s Minnesota 
(Appendix 8). The DSMB provides independent safety review and trial guidance during the 
ongoing trial. The DSMB will periodically meet to review the safety data and results across the 
treatment groups and will decide if the overall safety and feasibility of the trial remains acceptable. 
The DSMB will specifically review adverse event data as well as summary reports of all serious 
adverse events (SAEs) and may review individual cases if deemed appropriate or necessary to 
determine if a safety concern is emerging. The first meeting will take place after 50 participants 
have been enrolled or 6 months after recruitment begins and will meet at least annually thereafter.   
 
Stopping Rules and Data Safety Monitoring Plan 
The principal investigator and Data and Safety Monitoring Board (DSMB) will monitor data 
throughout the study and stop or amend the study if there is evidence of a lack of safety and/or 
efficacy. The members of DSMB are Drs. Stuart Winter, Mike Finch and Kelly Bergmann.  
 
Unblinding Procedures 
When the subject develops new symptoms or adverse event that need medical attention, the PI Dr, 
Madhok will refer to the randomization table to unblind subject.  
 
8.  Administrative Procedures 
Patient Confidentiality 
Data will be recorded in a customized REDCap database residing on the Children’s secure network. 
Access will be limited to the study team. All paper documents associated with the study will be kept 
in a locked file cabinet accessible only to the study team.  

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Data Management 
Data will be recorded in an electronic database residing on the Children’s secure network. Access 
will be limited to the study team. All paper documents associated with the study will be kept in a 
locked file cabinet accessible only to the study team. All study documents will be kept for at least 
three years. 
 
9.  References 
On-line Published Guidelines by Emergency Medical Services for Children at 
http://www.childrensnational.org/emsc/pubres/oldtoolboxpages/hospital-
based_performance_measures.aspx 
 
Ali S, Drendel AL, Kircher J, Beno S. Pain management of musculoskeletal injuries in children: 
current state and future directions. Pediatr Emerg Care. 2010 Jul;26(7):518-24; quiz 525-8. 
 
Boursinos LA, Karachalios T, Poultsides L, Malizos KN. Do steroids, conventional non-steroidal 
anti-inflammatory drugs and selective Cox-2 inhibitors adversely affect fracture healing? J 
Musculoskelet Neuronal Interact. 2009 Jan-Mar;9(1):44-52. 
 
Kouzi SA, Nuzum DS. Arnica for bruising and swelling. Am J Health Syst Pharm. 2007 Dec 
1;64(23):2434-43. 
 
Kotlus BS, Heringer DM, Dryden RM. Evaluation of homeopathic Arnica montana for ecchymosis 
after upper blepharoplasty: a placebo-controlled, randomized, double-blind study. Ophthalmic Plast 
Reconstr Surg. 2010 Nov-Dec;26(6):395-7. 
 
Paris A, Gonnet N, Chaussard C, Belon P, Rocourt F, Saragaglia D, Cracowski JL. Effect of 
homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre 
randomized placebo controlled study. Br J Clin Pharmacol. 2008 Feb; 65(2):180-7.  
 
Seeley BM, Denton AB, Ahn MS, Maas CS. Effect of homeopathic Arnica montana on bruising in 
face-lifts: results of a randomized, double-blind, placebo-controlled clinical trial. Arch Facial Plast 
Surg. 2006 Jan-Feb;8(1):54-9. 
 
Robertson A, Suryanarayanan R, Banerjee A. Homeopathic Arnica montana for post-tonsillectomy 
analgesia: a randomised placebo control trial. Homeopathy. 2007 Jan;96(1):17-21.  
 
Brinkhaus B, Wilkens JM, Lüdtke R, Hunger J, Witt CM, Willich SN. Homeopathic arnica therapy 
in patients receiving knee surgery: results of three randomised double-blind trials. Complement 
Ther Med. 2006 Dec;14(4):237-46. Epub 2006 Oct 13. 
 
Drendel AL, Gorelick MH, Weisman SJ, Lyon R, Brousseau DC, Kim MK. A randomized clinical 
trial of ibuprofen versus acetaminophen with codeine for acute pediatric arm fracture pain. Ann 
Emerg Med. 2009 Oct;54(4):553-60. 
 
Kayne, S.B., 2006. Homeopathic pharmacy: theory and practice. Elsevier Health Sciences. 

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Bellavite, P. and Signorini, A., 2002. The emerging science of homeopathy: complexity, 
biodynamics, and nanopharmacology. North Atlantic Books. 
 
10.  Appendix 
 
Appendix 1. Parent Take Home Table.  
Appendix 2. Instructions for use of homeopathic remedies  
Appendix 3. What is Homeopathy? 
Appendix 4. Parent Handout 
Appendix 5. REDCap form 
Appendix 6. Contact Information Sheet 
Appendix 7. RA Script 
Appendix 8. DSMB