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Study of Teriparatide in Stress Fracture Healing (RETURN)

Primary Purpose

Stress Fracture, Parathyroid Hormone

Status

Unknown status

Phase

Phase 3

Locations

United Kingdom

Study Type

Interventional

Intervention

Teriparatide

About this trial

This is an interventional treatment trial for Stress Fracture

Eligibility Criteria

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

Inclusion Criteria:

Signed informed consent form;
Participant must be aged 18 - 40 years inclusive;
Participant must have a lower limb stress fracture, either unilateral or bilateral, as confirmed via MRI scan;
Undergoing phase 1 or 2 training within an Army training establishment;
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.
Participants able to adhere to the visit schedule and protocol requirements.

Exclusion Criteria:

Hypersensitivity to the active Parathyroid Hormone substance or any of the excipients listed in the SmPC.
Pre-existing hypercalcaemia.
Patients with skeletal malignancies or bone metastases.
Any contraindications that would prevent the participant from undergoing an MRI scan.
Concurrent therapy that, in the investigators opinion, would interfere with the evaluation of the safety or efficacy of the study medication.
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.
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.
Metabolic bone diseases including hyperparathyroidism and Paget's disease of the bone.
Unexplained elevations of alkaline phosphatase.
Prior external beam or implant radiation therapy to the skeleton.
Patients participating in a concurrent drug trial.
Presentation with open epiphyses during the diagnostic MRI scan.
Participants with depression, as identified by completion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline.

Sites / Locations

Darlington Memorial HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention - Teriparatide Treatment

Control - Standard Care

Arm Description

Teriparatide 20ug/day from confirmation of stress fracture for 16 weeks, with the potential to extend to 24 weeks if required.

Standard rehabilitation care with additional monitoring to assess healing.

Outcomes

Primary Outcome Measures

Radiological healing.

Radiological healing by 2 Grades or more, or to grade zero at 8 weeks.

Secondary Outcome Measures

Radiological Healing

Time to complete radiological healing

Time from randomisation to assessed as 'Clinically Healed'.

Physical assessment to commence once the fracture is reported as healed on MR.

Time to 'Healing' as a composite assessment.

Healing as assessed by MRI and clinical assessment.

Time from randomisation to discharge from rehabilitation.

Completion of rehab will be assessed using Army standard measures.

Pain symptoms on a visual analogue pain scale.

Score between 0 and 10 - with 0 being no pain and 10 being worst pain imaginable.

Difference in Quality of life

Assessed by Short Form 36 Questionnaire. The higher score, the better the participants quality of life.

Adverse events

As reported in accordance with CTAE Version 4.03

Full Information

NCT ID

NCT04196855

First Posted

December 5, 2019

Last Updated

November 3, 2020

Sponsor

University of East Anglia

Collaborators

Ministry of Defence, United Kingdom, Darlington Memorial Hospital, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)

1. Study Identification

Unique Protocol Identification Number

NCT04196855

Brief Title

Study of Teriparatide in Stress Fracture Healing

Acronym

RETURN

Official Title

Study of Teriparatide in Stress Fracture Healing

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Unknown status

Study Start Date

December 23, 2019 (Actual)

Primary Completion Date

June 2022 (Anticipated)

Study Completion Date

October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of East Anglia

Collaborators

Ministry of Defence, United Kingdom, Darlington Memorial Hospital, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stress Fracture, Parathyroid Hormone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Masking Description

Blinded assessment of MR scans

Allocation

Randomized

Enrollment

136 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention - Teriparatide Treatment

Arm Type

Experimental

Arm Description

Teriparatide 20ug/day from confirmation of stress fracture for 16 weeks, with the potential to extend to 24 weeks if required.

Arm Title

Control - Standard Care

Arm Type

No Intervention

Arm Description

Standard rehabilitation care with additional monitoring to assess healing.

Intervention Type

Drug

Intervention Name(s)

Teriparatide

Other Intervention Name(s)

Terossa

Intervention Description

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.

Primary Outcome Measure Information:

Title

Radiological healing.

Description

Radiological healing by 2 Grades or more, or to grade zero at 8 weeks.

Time Frame

8 weeks.

Secondary Outcome Measure Information:

Title

Radiological Healing

Description

Time to complete radiological healing

Time Frame

8, 10, 12, 14, 16, 20, 24 weeks

Title

Time from randomisation to assessed as 'Clinically Healed'.

Description

Physical assessment to commence once the fracture is reported as healed on MR.

Time Frame

Twice weekly from date of radiologically healed stress fracture reported on MRI scan up to 24 weeks

Title

Time to 'Healing' as a composite assessment.

Description

Healing as assessed by MRI and clinical assessment.

Time Frame

Up to 24 weeks.

Title

Time from randomisation to discharge from rehabilitation.

Description

Completion of rehab will be assessed using Army standard measures.

Time Frame

Up to 24 weeks

Title

Pain symptoms on a visual analogue pain scale.

Description

Score between 0 and 10 - with 0 being no pain and 10 being worst pain imaginable.

Time Frame

Diary to be completed weekly and analysed as a change from baseline to 16 weeks (24 weeks in an unhealed fracture).

Title

Difference in Quality of life

Description

Assessed by Short Form 36 Questionnaire. The higher score, the better the participants quality of life.

Time Frame

4 weekly from baseline to 16 weeks

Title

Adverse events

Description

As reported in accordance with CTAE Version 4.03

Time Frame

Up to 28 weeks.

Other Pre-specified Outcome Measures:

Title

P1NP response to teriparatide treatment.

Description

Measurement of bone marker of formation.

Time Frame

Base line then 4 weekly to week 16 - extorted to week 24 in the case of an unhealed fracture.

Title

CTX response to teriparatide treatment.

Description

Measurement of bone marker of formation.

Time Frame

Base line then 4 weekly to week 16 - extorted to week 24 in the case of an unhealed fracture.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed informed consent form; Participant must be aged 18 - 40 years inclusive; Participant must have a lower limb stress fracture, either unilateral or bilateral, as confirmed via MRI scan; Undergoing phase 1 or 2 training within an Army training establishment; 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. Participants able to adhere to the visit schedule and protocol requirements. Exclusion Criteria: Hypersensitivity to the active Parathyroid Hormone substance or any of the excipients listed in the SmPC. Pre-existing hypercalcaemia. Patients with skeletal malignancies or bone metastases. Any contraindications that would prevent the participant from undergoing an MRI scan. Concurrent therapy that, in the investigators opinion, would interfere with the evaluation of the safety or efficacy of the study medication. 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. 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. Metabolic bone diseases including hyperparathyroidism and Paget's disease of the bone. Unexplained elevations of alkaline phosphatase. Prior external beam or implant radiation therapy to the skeleton. Patients participating in a concurrent drug trial. Presentation with open epiphyses during the diagnostic MRI scan. Participants with depression, as identified by completion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Katharine Law

Phone

+44 (0)1603 591222

katharine.law@uea.ac.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Alexander Carswell, Dr

a.carswell@uea.ac.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William Fraser, Dr

Organizational Affiliation

Norwich Medical School

Official's Role

Principal Investigator

Facility Information:

Facility Name

Darlington Memorial Hospital

City

Darlington

State/Province

County Durham

ZIP/Postal Code

DL3 6HX

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Rollins

Phone

01325 743366

First Name & Middle Initial & Last Name & Degree

Sivasamy Jambulingam

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34461961

Citation

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.

Results Reference

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Study of Teriparatide in Stress Fracture Healing

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