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Fracture Recovery for Returning to Duty (Teriparatide STRONG)

Primary Purpose

Stress Fracture, Fracture Healing, Military Training

Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Forteo Injectable Product
Placebo
Sponsored by
University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stress Fracture focused on measuring Military Training, Stress Fracture, Osteoanabolic, Rehabilitation

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Soldiers actively enlisted in the US Army attached to basic training unit at Fort Jackson who are 18 years of age or older.
  • Soldiers diagnosed with a diaphyseal tibial stress fracture
  • Skeletally mature
  • Willing to self-administer study medication
  • Desire to continue their military commitment and are willing to participate for the length of the project for up to one year.

Exclusion Criteria:

  • History of any form of cancer
  • Currently pregnant
  • Paget's disease of bone
  • Unexplained elevations of alkaline phosphatase (elevations in alkaline phosphatase may signal undiagnosed Paget's disease of bone)
  • Pediatric and young adult participants with open epiphyses
  • Prior external beam or implant radiation therapy involving the skeleton
  • Recent (within the last 6 months) urolithiasis (kidney stones)
  • Elevated serum calcium
  • Elevated uric acid
  • Orthostatic hypotension

Sites / Locations

  • Fort Jackson, SC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention with 28-day self-injection of Forteo

Placebo with 28-day self injection of inactive substance

Arm Description

The active study medication FORTEO is recombinant human parathyroid hormone analog, [rhPTH]. The study medication Forteo (teriparatide [rDNA origin] injection) (Eli-Lilly, Indiana, USA), will be self-administered via a blinded injection pen in the abdominal wall or thigh as described in the product guide. Subjects in the teriparatide arm will receive a 20 mcg dose of the medication daily for 28 days. Following this period the participant will receive standard physical therapy until full-return to duty.

Participants will self-administered a placebo substance normal in a replica, blinded, injection pen via in the abdominal wall or thigh daily for 28 days. Following this period the participant will receive standard physical therapy until full-return to duty.

Outcomes

Primary Outcome Measures

Days from diagnosis to full return to duty
This will be a time-based measure describing the total number of days of reduced duty associated with the diagnosis of tibial diaphyseal stress fracture. Between-group differences in this measure will be of key importance to determine the functional impact of the study drug compared to placebo.

Secondary Outcome Measures

Change from baseline in Tibial A-P and Lateral Radiographic Findings
Radiographs will be viewed by study physicians who will make a qualitative, visual estimate of the presence, or absence, of radiographic evidence of disruption of cortical bone in the tibial diaphysis. This judgement that will provide an estimate of clinical healing over time.
Change in Non-Contrast Tibial Magnetic Resonance Imaging Findings
Study physicians will use the Fredericson Classification to grade the magnitude of cortical bone and bone marrow involvement in the affected tibial diaphysis. This classification ranges from 0=Normal to 4b= the highest level of stress fracture (linear intra-cortical signal abnormality). Classifications using this scale have been demonstrated to have evidence of reliability and validity. This measure will provide an estimate of clinical healing over time.
Changes in activity performance measured by the Daily Activity Log
This log will be completed daily by the participant to provide an estimate of the likely loading and metabolic expenditure associated with his or her physical activity. 6 items will be sampled and evaluated individually. Three items will include distance (miles) from none to greater than 10 miles for marching, marching with combat gear, and running on that given day. The responses from these will be transformed to metabolic equivalent units (METS). One item will be categorical listing of the most stressful event of the day. The last 2 items will sample pain during activity and pain specific to walking using an 11 item 0-10 numeric rating scale. This measure will be used to assess the change in the participant's self report of activity tolerance over time.
Change in the Lower Extremity Functional Scale
The Lower Extremity Functional Scale (LEFS) is a commonly used self-report measure that reflects an individual's ability to perform several specific tasks that may be impaired by lower extremity dysfunction. 20 items are rated using a 5-point numeric rating scale (0= unable to perform; 4= no difficulty). The highest (best) score = 80% and indicates that the participant reports no difficulty performing activities. Measures obtained with the LEFS have strong evidence of reliability and longitudinal construct validity. This measure will be used to assess the change in the participant's self report of activity tolerance over time.
Change in DEXA scan scores
This measure will be used to generate a T-score that will provide a norm-referenced estimate of overall bone mass of the participant. A T-score of +1.0 to -1.0 would considered normal. -1.0 to - 2.5 would be considered as reduced and classified as osteopenia. A T-score < -2.5 would be considered severely reduced and classified as osteoporosis. This measure will used in secondary analysis to sub-classify individuals based upon bone mass at enrollment/inception and will be used to determine changes in overall bone mass upon completion of the study.

Full Information

First Posted
August 19, 2020
Last Updated
September 1, 2020
Sponsor
University of South Carolina
Collaborators
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04533984
Brief Title
Fracture Recovery for Returning to Duty (Teriparatide STRONG)
Official Title
Fracture Recovery for Returning to Duty (Teriparatide STRONG)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2020 (Anticipated)
Primary Completion Date
September 25, 2023 (Anticipated)
Study Completion Date
September 25, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of South Carolina
Collaborators
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
FORTEO (teriparatide [rDNA origin]; Eli-Lilly, Indiana, USA) is an injectable synthetic recombinant human parathyroid hormone analog that is commonly used to treat people with osteoporosis. In the current investigation this drug will be tested to evaluate its efficacy to accelerate bone healing and decrease the convalescence time of US Army Basic Trainees who have sustained a diaphyseal tibial stress fracture (DTSF). Investigators from the University of South Carolina will collaborate with military personnel to perform a prospective, randomized, double-blind, placebo-controlled study at Fort Jackson, SC.
Detailed Description
GOALS The project goals are to improve combat readiness of U.S. soldiers and sustain the availability of the military to deploy by, 1) decreasing the number of days not physically ready for duty after diagnosis of a stress fracture of the tibia, 2) decreasing the need for a physical profile or medical board after stress fracture of the tibia, and 3) decreasing the recurrence rates of these injuries. AIMS AND HYPOTHESES Specific Aim One is to determine the difference in the time from diagnosis to full return to activity for soldiers with diaphyseal tibia stress fracture who receive the teriparatide protocol compared to those who receive a placebo-control self-injection. This aim will be addressed by performing a prospective, longitudinal randomized, placebo-controlled trial in which 183 soldiers with acutely diagnosed diaphyseal tibia stress fractures will randomly receive a 1-month course of daily, self-injected 20 mcg. of teriparatide or daily, self-injected placebo. Hypothesis 1.1: Soldiers receiving teriparatide will return to duty 40% more quickly than those receiving placebo as measured in days from diagnosis to return to duty. Hypothesis 1.2: Following return to duty soldiers receiving teriparatide will be able to sustain a high daily duty load as measured in metabolic equivalents (METs) on a daily training log. Specific Aim Two is to determine the long-term effects of the administration of teriparatide. Study participants will be followed for 1-year after the completion of the study drug year to determine the incidence of drug related side effects, injury recurrence and/or additional bone stress injury based on data from the participants' Electronic Medical Record. Hypothesis 2.1: Soldiers receiving teriparatide will have a reduced rate of new and/or recurrent bone stress injuries as measured by their need for a military physical profile due to bone stress injuries and/or their medical record diagnosis of a bone stress injury than those treated with placebo. Hypothesis 2.2: Soldiers receiving teriparatide will be more likely to complete their first assigned station as measured by a medical discharge board than those treated with placebo. Hypothesis 2.3: Soldiers receiving teriparatide will have a high bone mass as measured by DEXA scan age matched t-score than those treated with placebo than those treated with placebo. RECRUITMENT AND SCREENING OF PARTICIPANTS Soldiers who have pain in the mid-tibia area while in basic training at Ft. Jackson, SC report to Moncrief Medical Clinic where they are medically evaluated by their Primary Care Manager (PCM). The injured soldiers would have further diagnostic testing in the form of anterior-posterior (A-P) and lateral view radiographs of the tibia followed by a radio-nucleotide bone scan if indicated. Soldiers found to have a DTSF report to the physical therapy department for further evaluation and treatment. The physical therapist will notify the embedded research nurse coordinator of a new soldier who has a DSTF and will initiate a pre-screen for study participation. If the DTSF and resulting functional limitation is so severe to require convalescent leave, the research nurse coordinator will be notified and will approach the patient to provide general information about the study and invite the patient to learn more about potential participation. For patients who are interested in participating, the research nurse coordinator will initiate the informed consent process. All study risks and potential benefits will be discussed with the patient. Informed consent information and discussion will include information about the need to self-administer the study medication. Once a fully executed informed consent document has been signed, the research nurse coordinator will initiate the study screening visit that will require participants to complete a medical questionnaire to assess eligibility based on their personal medical history. An initial blood draw will be obtained that will assess suitability for initiating therapy with teriparatide, including lab values within the following ranges: Total serum calcium (normal range 8.5-10.2 mg/dL) Total serum alkaline phosphatase: (normal range 44 to 147 IU/L) 25-hydroxyvitamin D: (normal range 20 and 40 ng/mL) Parathyroid Hormone: (normal - 10-65 pig/mL or 10-65 ng/L) Creatinine clearance: (normal 88-128 mL/min for healthy women or 97-137 mL/min for healthy men) Serum qualitative urine pregnancy test (females): negative Serum uric acid: (normal 2.4-6.0 mg/dL. (female) and 3.4 - 7.0 mg/dL. (male). Individuals with laboratory results outside of the normal range will be excluded from further study procedures and will be ineligible to participate in further study procedures including being ineligible to be randomized or receive study drug. To assess bone mass, a bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) of the lumbar spine and bilateral hips will be performed. Additional inclusion and exclusion criterion are described below. Results from the screening visit will be reviewed by the medical monitoring team and investigators, who will make the final decision regarding the patient's eligibility for inclusion in the study. RANDOMIZATION AND GROUP ASSIGNMENT Upon completion of the screening visit if the consenting soldier is found eligible for the study, the participant would then be randomized via computer generated block randomization performed by the research nurse coordinator. There will be a 1:1 randomization into either the placebo arm or the 20 mcg teriparatide treatment arm. The Pharmacist of Record would then record which study arm into which the patient was randomized, dispense the appropriate blinded medication (active study drug vs placebo) to the research nurse and store the assigned information securely using an encrypted data base. The injection pens will be blinded to the patient, the research nurse coordinator, and the staff at Ft. Jackson. If an emergency in patient care arises, any medical staff treating the patient can request un-blinding by calling the research team. The investigative team will be immediately informed of any such requests to ensure safety of the study subject. INTERVENTION Following group assignment, the study participant will have a meeting with the research nurse to be instructed on care and handling of the medication. The participant will then directly observe the first administration of the medication to ensure safe and effective administration and remind the subject/participant to alternate injection sites such as the abdomen or leg as well as not injecting in same spot on the abdomen or leg each day to avoid bruising. Next the participant will be a given 28 tablets of 500 mg Calcium to take orally. The participants will then leave Ft. Jackson and return home for convalescent leave. The participant will self-administer the mediation daily via injection pen and will receive a weekly call from the research nurse to ensure study medication compliance and monitor for any adverse events. Upon return from 30 days of convalescent leave, participants will report back to Ft. Jackson and begin the reattachment process to their unit. At this time, the participant will have another peripheral venous blood draw to evaluate calcium level. Participants will then transition into the active rehabilitation phase of the study in which they will report daily to the physical therapy department on Ft. Jackson for treatment, per the standard of care. During their scheduled reporting at physical therapy, participants will complete a training log of their previous day's activities. This will allow for a day-to-day tracking of physiologic load. They will continue to advance the training and activity as tolerated based on their pain and guidance from the physical therapist until the participant successfully completes the Army Combat Fitness Test (ACFT) which will qualify them for return to duty. Once participants have matriculated through basic training, they will receive their initial duty station. Their military record, including physical profile (limited duty) status, new or recurrent bone stress injury diagnosis, the need to convene a medical discharge board or successful uninterrupted completion of their duty station will be monitored and recorded. To determine the long-term effects of the administration of teriparatide, study enrollees will be followed for 1-year post study drug year. this follow-up is to determine the incidence of drug-related side effects, injury recurrence and/or additional bone stress injury based on data from the participants' Electronic Medical Record.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stress Fracture, Fracture Healing, Military Training
Keywords
Military Training, Stress Fracture, Osteoanabolic, Rehabilitation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Prospective, Randomized, Placebo-Controlled, Double-Blind Clinical Trial
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
183 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention with 28-day self-injection of Forteo
Arm Type
Experimental
Arm Description
The active study medication FORTEO is recombinant human parathyroid hormone analog, [rhPTH]. The study medication Forteo (teriparatide [rDNA origin] injection) (Eli-Lilly, Indiana, USA), will be self-administered via a blinded injection pen in the abdominal wall or thigh as described in the product guide. Subjects in the teriparatide arm will receive a 20 mcg dose of the medication daily for 28 days. Following this period the participant will receive standard physical therapy until full-return to duty.
Arm Title
Placebo with 28-day self injection of inactive substance
Arm Type
Placebo Comparator
Arm Description
Participants will self-administered a placebo substance normal in a replica, blinded, injection pen via in the abdominal wall or thigh daily for 28 days. Following this period the participant will receive standard physical therapy until full-return to duty.
Intervention Type
Drug
Intervention Name(s)
Forteo Injectable Product
Other Intervention Name(s)
Standard rehabilitation exercises which are the same for both groups; 500 mg of Calcium PO each day for both groups
Intervention Description
Forteo Injectable Product
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Self-injection of sterile saline
Primary Outcome Measure Information:
Title
Days from diagnosis to full return to duty
Description
This will be a time-based measure describing the total number of days of reduced duty associated with the diagnosis of tibial diaphyseal stress fracture. Between-group differences in this measure will be of key importance to determine the functional impact of the study drug compared to placebo.
Time Frame
Spans from time of enrollment until return to full-duty. This could range from 12 weeks to 24 weeks
Secondary Outcome Measure Information:
Title
Change from baseline in Tibial A-P and Lateral Radiographic Findings
Description
Radiographs will be viewed by study physicians who will make a qualitative, visual estimate of the presence, or absence, of radiographic evidence of disruption of cortical bone in the tibial diaphysis. This judgement that will provide an estimate of clinical healing over time.
Time Frame
Follow-up films will be obtained in post-enrollment weeks 4, 12, 16, and 48
Title
Change in Non-Contrast Tibial Magnetic Resonance Imaging Findings
Description
Study physicians will use the Fredericson Classification to grade the magnitude of cortical bone and bone marrow involvement in the affected tibial diaphysis. This classification ranges from 0=Normal to 4b= the highest level of stress fracture (linear intra-cortical signal abnormality). Classifications using this scale have been demonstrated to have evidence of reliability and validity. This measure will provide an estimate of clinical healing over time.
Time Frame
Follow-up images will be obtained in weeks 4, 12, and 48
Title
Changes in activity performance measured by the Daily Activity Log
Description
This log will be completed daily by the participant to provide an estimate of the likely loading and metabolic expenditure associated with his or her physical activity. 6 items will be sampled and evaluated individually. Three items will include distance (miles) from none to greater than 10 miles for marching, marching with combat gear, and running on that given day. The responses from these will be transformed to metabolic equivalent units (METS). One item will be categorical listing of the most stressful event of the day. The last 2 items will sample pain during activity and pain specific to walking using an 11 item 0-10 numeric rating scale. This measure will be used to assess the change in the participant's self report of activity tolerance over time.
Time Frame
This will be completed daily between post-enrollment weeks 4-17. It will be completed once in week 48
Title
Change in the Lower Extremity Functional Scale
Description
The Lower Extremity Functional Scale (LEFS) is a commonly used self-report measure that reflects an individual's ability to perform several specific tasks that may be impaired by lower extremity dysfunction. 20 items are rated using a 5-point numeric rating scale (0= unable to perform; 4= no difficulty). The highest (best) score = 80% and indicates that the participant reports no difficulty performing activities. Measures obtained with the LEFS have strong evidence of reliability and longitudinal construct validity. This measure will be used to assess the change in the participant's self report of activity tolerance over time.
Time Frame
This will be completed weekly during post-enrollment weeks 4-17. It will be completed once in week 48
Title
Change in DEXA scan scores
Description
This measure will be used to generate a T-score that will provide a norm-referenced estimate of overall bone mass of the participant. A T-score of +1.0 to -1.0 would considered normal. -1.0 to - 2.5 would be considered as reduced and classified as osteopenia. A T-score < -2.5 would be considered severely reduced and classified as osteoporosis. This measure will used in secondary analysis to sub-classify individuals based upon bone mass at enrollment/inception and will be used to determine changes in overall bone mass upon completion of the study.
Time Frame
Post-enrollment week 16. This will be compared to baseline (week 1) images

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Soldiers actively enlisted in the US Army attached to basic training unit at Fort Jackson who are 18 years of age or older. Soldiers diagnosed with a diaphyseal tibial stress fracture Skeletally mature Willing to self-administer study medication Desire to continue their military commitment and are willing to participate for the length of the project for up to one year. Exclusion Criteria: History of any form of cancer Currently pregnant Paget's disease of bone Unexplained elevations of alkaline phosphatase (elevations in alkaline phosphatase may signal undiagnosed Paget's disease of bone) Pediatric and young adult participants with open epiphyses Prior external beam or implant radiation therapy involving the skeleton Recent (within the last 6 months) urolithiasis (kidney stones) Elevated serum calcium Elevated uric acid Orthostatic hypotension
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
F F Beattie, PhD
Phone
803-447-1589
Email
pbeattie@mailbox.sc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
James B Jackson, MD
Phone
704-287-3882
Email
Benjamin.Jackson@prismahealth.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James B Jackson, MD
Organizational Affiliation
Principal Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fort Jackson, SC
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29207
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lorri Gibbons, RN
Phone
803-315-4655
Email
Lorrigibbons@uscmed.sc.edu
First Name & Middle Initial & Last Name & Degree
Paul F Beattie, PhD
Phone
8034471589
Email
pbeattie@mailbox.sc.edu
First Name & Middle Initial & Last Name & Degree
James B Jackson, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Fracture Recovery for Returning to Duty (Teriparatide STRONG)

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