Study of Teriparatide in Stress Fracture Healing (RETURN)

Investigation into the use of teriparatide in the treatment of stress fractures.

Primary outcome is healing on MRI, secondary outcomes are pain, time spent in rehabilitation and future stress fractures. This study will help the investigators understand how to treat stress fractures in the future.

Study Overview

• Status: Unknown
• Conditions: Stress Fracture; Parathyroid Hormone
• Intervention / Treatment: Drug: Teriparatide

Detailed Description

Teriparatide is a drug that is designed to have a similar effect on the body as parathyroid hormone. Parathyroid hormone is made naturally in the body and is released in response to low calcium levels. It helps to maintain bone health and repair bone damage. Parathyroid hormone and medicines like teriparatide can strengthen bones and are often given to people with osteoporosis (a condition that weakens bones, making them more likely to break) to reduce the risk of fractures. Recent studies have also shown benefits in people with stress fracture injuries, a form of bone damage sometimes caused by repetitive exercise. The investigators want to know if teriparatide is also beneficial to healthy, younger people who have a stress fracture injury.

• Study Type: Interventional
• Enrollment (Anticipated): 136
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • County Durham
    • Darlington, County Durham, United Kingdom, DL3 6HX
      • Recruiting
      • Darlington Memorial Hospital
      • Contact: David Rollins; Phone Number: 01325 743366
      • Principal Investigator: Sivasamy Jambulingam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent form;
2. Participant must be aged 18 - 40 years inclusive;
3. Participant must have a lower limb stress fracture, either unilateral or bilateral, as confirmed via MRI scan;
4. Undergoing phase 1 or 2 training within an Army training establishment;
5. Blood Tests within reference range. Minor abnormalities will be assessed by the PI. Patients will still be entered if these are felt to be of no clinical importance.
6. Participants able to adhere to the visit schedule and protocol requirements.

Exclusion Criteria:

1. Hypersensitivity to the active Parathyroid Hormone substance or any of the excipients listed in the SmPC.
2. Pre-existing hypercalcaemia.
3. Patients with skeletal malignancies or bone metastases.
4. Any contraindications that would prevent the participant from undergoing an MRI scan.
5. Concurrent therapy that, in the investigators opinion, would interfere with the evaluation of the safety or efficacy of the study medication.
6. Pregnancy, suspected pregnancy or breastfeeding. Female participants must have a negative serum pregnancy test at screening and be willing and able to use a "highly effective" method of contraception, as per the Clinical Trial Facilitation Group (CTFG) guidance.
7. Severe renal impairment. Participants with moderate renal impairment will be treated with caution at the Principal Investigator's discretion and in accordance with the SmPC.
8. Metabolic bone diseases including hyperparathyroidism and Paget's disease of the bone.
9. Unexplained elevations of alkaline phosphatase.
10. Prior external beam or implant radiation therapy to the skeleton.
11. Patients participating in a concurrent drug trial.
12. Presentation with open epiphyses during the diagnostic MRI scan.
13. Participants with depression, as identified by completion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention - Teriparatide Treatment; Teriparatide 20ug/day from confirmation of stress fracture for 16 weeks, with the potential to extend to 24 weeks if required.	Drug: Teriparatide; Terrosa 20 micrograms/80 microliters solution for injection. Each dose of 80 microliters contains 20 micrograms of teriparatide. One cartridge of 2.4 mL of solution contains 600 micrograms of teriparatide (corresponding to 250 micrograms per mL). Teriparatide, rhPTH(1-34), produced in E. coli, using recombinant DNA technology, is identical to the 34-N-terminal amino acid sequence of endogenous human parathyroid hormone.; Other Names: Terossa
No Intervention: Control - Standard Care; Standard rehabilitation care with additional monitoring to assess healing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological healing.	Radiological healing by 2 Grades or more, or to grade zero at 8 weeks.	8 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological Healing	Time to complete radiological healing	8, 10, 12, 14, 16, 20, 24 weeks
Time from randomisation to assessed as 'Clinically Healed'.	Physical assessment to commence once the fracture is reported as healed on MR.	Twice weekly from date of radiologically healed stress fracture reported on MRI scan up to 24 weeks
Time to 'Healing' as a composite assessment.	Healing as assessed by MRI and clinical assessment.	Up to 24 weeks.
Time from randomisation to discharge from rehabilitation.	Completion of rehab will be assessed using Army standard measures.	Up to 24 weeks
Pain symptoms on a visual analogue pain scale.	Score between 0 and 10 - with 0 being no pain and 10 being worst pain imaginable.	Diary to be completed weekly and analysed as a change from baseline to 16 weeks (24 weeks in an unhealed fracture).
Difference in Quality of life	Assessed by Short Form 36 Questionnaire. The higher score, the better the participants quality of life.	4 weekly from baseline to 16 weeks
Adverse events	As reported in accordance with CTAE Version 4.03	Up to 28 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
P1NP response to teriparatide treatment.	Measurement of bone marker of formation.	Base line then 4 weekly to week 16 - extorted to week 24 in the case of an unhealed fracture.
CTX response to teriparatide treatment.	Measurement of bone marker of formation.	Base line then 4 weekly to week 16 - extorted to week 24 in the case of an unhealed fracture.

Collaborators and Investigators

• Sponsor: University of East Anglia
• Collaborators: Ministry of Defence, United Kingdom; Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK); Darlington Memorial Hospital
• Investigators: Principal Investigator: William Fraser, Dr, Norwich Medical School

Publications and helpful links

General Publications

• Carswell AT, Eastman KG, Casey A, Hammond M, Shepstone L, Payerne E, Toms AP, MacKay JW, Swart AM, Greeves JP, Fraser WD. Teriparatide and stress fracture healing in young adults (RETURN - Research on Efficacy of Teriparatide Use in the Return of recruits to Normal duty): study protocol for a randomised controlled trial. Trials. 2021 Aug 30;22(1):580. doi: 10.1186/s13063-021-05556-3.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2019
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Stress; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: 19/HRA/6011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No