Clinical trial NCT03812991
Conditions: Pelvic Ring Fractures
Sponsor: University of Missouri-Columbia
Start date: 2019-07-01; Completion date: 2023-02-28
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Pelvic ring fractures in the geriatric population are a rising problem for surgeons in industrialized countries. Many of these low-energy fractures are treated nonoperatively; however, pain is a significant factor in recovery of these patients and often inhibits their ability to mobilize. Most of these fractures are lateral compression type 1 injuries which are defined as an impaction to the sacrum with varying amounts of anterior/pubic root/rami fractures. Many of these patients in the geriatric population suffer from osteoporosis and the injuries are often sustained from a low-energy mechanism like a fall. The tenet of treatment for all osteoporotic fractures is early mobilization. It is well known that extended periods of bed rest will lead to pneumonia, decubitus ulceration, deep venous thrombosis, and, in the case of the pelvis, not prevent subsequent deformity. Calcitonin is a polypeptide containing 32 amino acids, and it plays a role in the regulation of bone metabolism as a hormone that prevents bone resorption. Intranasal salmon calcitonin (ISC) has been demonstrated to decrease pain and improve the level of activity in patients with acute vertebral osteoporotic compression fractures when administered within the first 5 days of onset of pain/injury. It has also demonstrated an immediate post analgesic effect in osteoporotic distal radius fractures treated nonoperatively. The antihyperalgesic action of calcitonin appears to be mediated by serotonin receptors. The purpose of this study is to evaluate the analgesic effect of ISC on geriatric patients with pelvic ring injuries who are treated nonoperatively.

Detailed description:
Baseline: Treatment group will be prescribed 200IU of ISC daily for a period of 3 months. The control group will not be prescribed calcitonin. Participants will complete research only Iowa pelvis score questionnaire, SF-36 questionnaire and visual analogue scale (VAS) to assess subjective pain and function. Two-week follow up visit post discharge: participants will complete Iowa pelvis score questionnaire, SF-36 questionnaire and VAS to assess subjective pain and function. Participants will be referred for a standard of care DEXA bone density scan if they have no previous diagnosis of osteoporosis and no history of previous scan within a year. Six weeks post discharge: participants will complete Iowa pelvis score questionnaire, SF-36 questionnaire and VAS to assess subjective pain and function. Participants will undergo standard of care radiographic analysis of pelvic ring injury with AP/inlet and outlet pelvic x-rays 4. Twelve weeks post discharge: Participants will complete Iowa pelvis score questionnaire, SF-36 questionnaire and VAS to assess subjective pain and function. Participants will undergo standard of care radiographic analysis of pelvic ring injury with AP/inlet and outlet pelvic x-rays - Participants will perform a timed up and go (TUG) test.

After informed consent is obtained, all patients who meet eligibility criteria will be randomized into one of two groups. Randomization will be achieved by numbering 50 sealed white envelopes (25 control, 25 treatment). There is no blinding to the randomization. It would be difficult to blind the participants, or the research personnel. We do not believe there will be any significant bias that can be corrected with blinding.

Treatment: 200IUof ISC daily for a period of 3 month

Control: Will not be prescribed calcitonin (ISC)

Arms: arm 1: This is the Non-Treatment Arm of the study. No intervention is to be administered. arm 2: 1 spray (200 IU) qDay, alternate nostrils daily
Interventions: intervention 1: Miacalcin Calcitonin Salmon Nasal Spray
Intervention descriptions: intervention 1: Miacalcin nasal spray is 1 spray (200 International Units) per day administered intranasally, alternating nostrils daily

Protocol documents:
Prot_001.pdf: 
Page 1 of 6 
BIOMEDICAL RESEARCH PROTOCOL  
UNIVERSITY OF MISSOURI 
 
Project Title: The Use of Intranasal Calcitonin to Improve Pain and Activity in Elderly Pelvic 
Ring Injuries 
IRB Number: 2013172 
Version Number: 2 
Version Date: 09/13/2019 
Principal Investigator: Brett D. Crist, MD 
Funding Source: AOTNA Grant             
 
 
 
 
1. Include primary, secondary, and exploratory objectives.  
Primary Objective: To compare acute pain over a three-month period in geriatric patients 
with pelvic ring injuries who receive intranasal salmon calcitonin with those who do not 
receive intranasal salmon calcitonin 
Secondary Objective: To compare function and activity over a three-month period in 
geriatric patients with pelvic ring injuries who are treated nonoperatively and receive 
intranasal salmon calcitonin with those who do not receive intranasal salmon calcitonin. 
Exploratory objective: To compare radiographic healing in geriatric patients with pelvic 
ring injuries who receive intranasal salmon calcitonin with those who do not receive 
intranasal salmon calcitonin 
2. Include background and rationale for initiating the study. Includes pre-clinical and 
clinical data, current experiences with procedures, drug, or device, and any other relevant 
information to justify the research. 
It is anticipated that geriatric patients who sustain pelvic ring injuries and are 
treated nonoperatively will demonstrate decreased pain scores and improved 
subjective and objective function if they are started on intranasal salmon calcitonin 
within 5 days of injury compared to patients who do not receive intranasal salmon 
calcitonin. It is anticipated the decreased pain and improved activity/function will 
prevent complications associated with extended periods of bedrest. 
 
 
 
 
1. Include the product, dose, route, and regimen.  
200 IU of ISC(intranasal salmon calcitonin) daily for three months 
 
2. Include the rationale for choosing the drug/biologic and dose, or for choosing the device 
to be used. 
Intranasal salmon calcitonin (ISC) has been demonstrated to decrease pain and improve 
the level of activity in patients with acute vertebral osteoporotic compression fractures 
when administered within the first 5 days of onset of pain/injury. Recently, randomized 
I. 
Research Objectives/Background 
II. 
Drugs/Biologics/Devices 


Page 2 of 6 
clinical trials have demonstrated calcitonin to be superior to NSAIDS in promoting early 
ambulation and preventing functional deterioration in patients with acute osteoporotic 
vertebral compression fractures. 
2. Include the standard reference therapy against which the study product is being 
compared, or if the reference is a placebo. Include justification for inclusion of a placebo 
or non-treatment group. The study product is being compared to geriatric patients who 
are being treated nonoperatively and receive standard of care that does not include 
intranasal salmon calcitonin. Many geriatric patients with pelvic ring injuries who are treated 
nonoperatively. However, all patients will be prescribed calcium and vitamin D supplementation. 
 
 
 
1. Describe the recruitment process; including how and where recruitment will take place. 
Recruitment will take place in the Emergency Room or at University of Missouri Main 
Hospital. Patients who have pelvic ring injuries will be screened for enrollment.  
2. Describe any screening/baseline procedures. 
Patients will be screened by an attending orthopaedic traumatologist determining the type 
of pelvic ring injury based on x-rays and CT scans and decide upon operative treatment 
vs. nonoperative treatment. Patients who are deemed to benefit from nonoperative 
treatment will be screened for enrollment. Any patients who meet the criteria for age will 
then be further screened for inclusion and exclusion criteria as outlined below. 
 
 
 
 
1. Describe the consent process; including who will be approached for consent and what 
type of consent will be obtained from each subject population, if there is more than one. 
Study personnel will approach patient about research study in the emergency room or on 
the designated floor where they are admitted. Informed consent will be obtained at that 
time. 
 
 
 
1. List the inclusion and exclusion criteria.  
2. Inclusion:  
• Males or females over the age of 65 who sustain isolated pelvic ring injuries via a 
low-energy mechanism. 
 
Exclusion:  
• An open pelvic ring fracture  
• Concomitant acetabular fracture  
• They are on ISC prior to enrollment 
• Use of medications for the treatment or prevention of Osteoporosis with the 
exemption of Vitamin D and Calcium supplementation  
• Allergic or have contraindications to calcitonin or salmon  
III. 
Recruitment Process 
IV. 
Consent Process 
V. 
Inclusion/Exclusion Criteria 


Page 3 of 6 
• Sustain other injuries in their spine (excluding transverse and spinous 
process fractures) or lower extremities  
• Unwilling to participate in the study  
• Nonambulatory at baseline  
• Neurologic deficit associated with the pelvic ring injury 
3. Describe restrictions on participation and appropriate screening procedures to ensure that 
the restrictions are maintained, including pregnancy testing. 
• All patients meeting inclusion criteria will be screened by study personnel.   
 
 
 
 
1. Include anticipated enrollment number in this study. Include a break-down in numbers if 
there is more than one subject population. 
• 60 patients; 25 each group; 10 screen fails 
2. Include statistical analysis or other justification for the number of subjects enrolled.  
 
 
 
 
 
 
1. Include study procedures/design/plan; include the sequence and timing of study 
procedures (distinguish research procedures from those that are part of routine care). 
Include study duration and number of study visits required. 
After obtaining informed consent, the following will be obtained:  
 
Baseline: Treatment group will be prescribed 200IU of ISC daily for a period of 3 
months. The control group will not be prescribed calcitonin. Participants will 
complete research only Iowa pelvis score questionnaire, SF-36 questionnaire and 
visual analogue scale (VAS) to assess subjective pain and function. Two-week 
follow up visit post discharge: participants will complete Iowa pelvis score 
questionnaire, SF-36 questionnaire and VAS to assess subjective pain and function. 
Participants will be referred for a standard of care DEXA bone density scan if they 
have no previous diagnosis of osteoporosis and no history of previous scan within a 
year. Six weeks post discharge:  participants will complete Iowa pelvis score 
questionnaire, SF-36 questionnaire and VAS to assess subjective pain and function. 
Participants will undergo standard of care radiographic analysis of pelvic ring 
injury with AP/inlet and outlet pelvic x-rays 4. Twelve weeks post discharge:  
Participants will complete Iowa pelvis score questionnaire, SF-36 questionnaire 
and VAS to assess subjective pain and function. Participants will undergo standard 
of care radiographic analysis of pelvic ring injury with AP/inlet and outlet pelvic x-
rays - Participants will perform a timed up and go (TUG) test. 
 
2. Blinding, including justification for blinding or not blinding the trial. Describe un-
blinding procedures.  
VI. 
Number of Subjects 
VII. 
Study Procedures/ Design/Treatment Plan 


Page 4 of 6 
After informed consent is obtained, all patients who meet eligibility criteria will be 
randomized into one of two groups. Randomization will be achieved by numbering 50 
sealed white envelopes (25 control, 25 treatment). There is no blinding to the 
randomization. It would be difficult to blind the participants, or the research personnel. 
We do not believe there will be any significant bias that can be corrected with blinding.  
 
 
Treatment: 200IUof ISC daily for a  period of 3 month 
 
Control: Will not be prescribed calcitonin (ISC) 
 
3. Justification of why participants will not receive routine care or will have current therapy 
stopped.  
Patients will receive routine care during this study.  
4. Definition of treatment failure or participant removal criteria. 
Patients will be removed if they do not return to their follow-up visits or do not complete 
the study specific tasks.  
5. Description of what happens to participants receiving therapy when study ends or if 
participation in the study ends prematurely. 
Routine care will continue per the physician’s standard of care treatment.  
6. Include sub-studies or banking information (correlative/special studies) 
None 
 
 
1. Describe reasonably foreseeable risks or discomforts to the subjects and steps to 
minimize risks. This study is expected to have minimal risk to the patient since we are 
using the FDA approved dosage for this study. This risk will be minimized by going over 
the purpose of the study with the patient before obtaining consent, and allowing 
withdrawal from the study at any time. 
 
2. Describe any stopping rules. Stopping rules would include any reactions or side effects to 
ISC or per the provider’s discretion.  
 
3. Include the plan for reporting unanticipated problems or deviations. This plan must 
include a five-day reporting requirement to the IRB once becoming aware of an event.  
 
 
 
 
 
 
 
1. Include both direct and indirect benefits for either the individual or society.  
The benefit to society is to provide data that will eventually lead to decrease pain in 
patients with pelvic ring fractures by using intranasal Calcitonin within 5 days of injury.  
VIII. Potential Risks/Adverse Events 
IX. 
Anticipated Benefits 


Page 5 of 6 
No direct benefits will be promised.  Subjects can expect to help add to public knowledge 
about the effect of pelvic rings fractures in elderly patients.  
 
 
 
 
 
1. Describe the amount, method, and timing of disbursement.  Compensation can include 
checks, cash, gifts, extra/course credit, etc.  
Subjects will be paid $10 for each visit they complete but will only receive one check 
once they finish their 12 week visit.  Subjects will be paid $30 at their final visit.  
 
 
 
 
1. Detail costs of study procedures, drugs, biologics, or devices and identify who will cover 
the cost. All costs are being covered by the AOTNA grant. No additional costs to the 
participants for being enrolled in the study. Participants will pay for all standard of care 
costs.  
 
Cost:  
$1,800 – Calcitonin Costs ($72 per participant x 25 participants) 
$1,500 – Participant Stipend ($30 per participant x 50 participants) 
$6,500 – Study Coordinator (0.7 calendar months, 5.9% effort, of assistance, covering salary and 
benefits for this effort) 
Total: $9,800 
 
 
 
 
Describe the plan to monitor the data, if necessary. A plan is required for treatment and/or 
intervention studies, sensitive data are being collected, there is a possibility for subjects to 
experience adverse events, etc. Adverse events will be reported to the IRB as necessary within 5 days 
of becoming aware of the event. 
1. The plan should include when something needs to be reported 
2. The frequency of the monitoring, such as points in time or after a specific number of 
participants are enrolled 
3. Who will conduct the monitoring, such as a data board, medical monitor, investigator, 
independent physician; the specific data to be monitored 
4. Procedures for analysis and interpretation of the data 
5. Actions to be taken upon specific events or end points  
6. Procedures for communication from the data monitor to this site. 
 
 
 
 
X. 
Compensation 
XII. 
Data Safety Monitoring Plan 
XIV. References/Appendices 
XI. 
Costs 
 


Page 6 of 6 
 
1. Include findings from a literature search or pilot study must be outlined including 
appropriate detailed references to earlier studies and data.  
 
1. Karponis A, Rizou S, Pallis D, Zafeiris CP, Georgiou DF, Galanos A, Giannoulis 
F, Lyritis GP. Analgesic effect of nasal salmon calcitonin during the early post-
fracture period of the distal radius fracture. J Musculoskelet Neuronal Interact. 
2015 Jun;15(2):186-9. 
2.  Knopp JA, Diner BM, Blitz M, Lyritis GP, Rowe BH. Calcitonin for 
treating acute pain of osteoporotic vertebral compression fractures: a 
systematic review of randomized, controlled trials. Osteoporos Int. 2005 
Oct;16(10):1281-90. 
3. Lyritis GP, Paspati I, Karachalios T, Ioakimidis D, Skarantavos G, Lyritis 
PG. Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush 
fractures. A double blind, placebo-controlled clinical study. Acta Orthop 
Scand Suppl. 1997 Oct;275:112-4.  
4.  Lyritis GP, Tsakalakos N, Magiasis B, Karachalios T, Yiatzides A, 
Tsekoura M. Analgesic effect of salmon calcitonin in osteoporotic vertebral 
fractures: a double-blind placebo- controlled study. Calcif Tissue Int. 1991 
Dec;49(6):369-72.  
5. 5. Hoch A, Ozkurtul O, Pieroh P, Josten C, Bohme, J. Outcome and 2-Year 
Survival Rate in Elderly Patients With Lateral Compression Fractures of the 
Pelvis. Geriatr Orthop Surg Rehabil. 2017 Mar;8(1):3-9. 
6. Leslie MP, Baumgaertner MR. Osteoporotic pelvic ring injuries. Orthop 
Clin North Am. 2013 Apr;44(2):217-24. Review. 
7. Henriksen K, Byrjalsen I, Andersen JR, Bihlet AR, Russo LA, 
Alexandersen P, Valter I, Qvist P, Lau E, Riis BJ, Christiansen C, Karsdal   
MA; SMC021 investigators. A randomized, double-blind, multicenter, 
placebo-controlled study to evaluate the efficacy and safety of oral salmon 
calcitonin in the treatment of osteoporosis in postmenopausal women taking 
calcium and vitamin D. Bone. 2016 Oct;91:122-9.  
8.  Endo N, Fujino K, Doi T, Akai M, Hoshino Y, Nakano T, Iwaya T. Effect 
of elcatonin versus nonsteroidal anti-inflammatory medications for acute 
back pain in patients with osteoporotic vertebral fracture: a multiclinic 
randomized controlled trial. J Bone Miner Metab. 2017 Jul;35 (4):375-384.  
9. Ito A, Yoshimura M. Mechanisms of the analgesic effect of calcitonin on 
chronic pain by alteration of receptor or channel expression. Mol Pain. 2017 
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10. Yoshimura M, Furue H, Ito A. Anti-nociceptive effect of calcitonin on 
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11. Ito A, Furue H, Yoshimura M. Recent insights into mechanisms for 
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