Stress FracturePhase 3RETURNNCT04196855
Study of Teriparatide in Stress Fracture Healing
A Phase 3 study testing Teriparatide in people with Stress Fracture and Parathyroid Hormone, run by University of East Anglia at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Stress Fracture, Parathyroid Hormone
- What is being tested?
- Teriparatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Dec 2019to Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Alexander Carswell, Dr contact
United Kingdom1 site, 1 recruiting
- Recruiting
Darlington Memorial Hospital
Darlington, County Durham, DL3 6HX
David Rollins, 01325 743366
Sivasamy Jambulingam
About this study
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.
Read the 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.
- Conditions
- Stress Fracture, Parathyroid Hormone
- Being tested
- Teriparatide
- Medical subject headings
- Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TeriparatideDrug
Also called Terossa
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention - Teriparatide Treatment | Experimental | Teriparatide 20ug/day from confirmation of stress fracture for 16 weeks, with the potential to extend to 24 weeks if required. Receives: Drug: Teriparatide |
| Control - Standard Care | No intervention | Standard rehabilitation care with additional monitoring to assess healing. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiological healing.
Radiological healing by 2 Grades or more, or to grade zero at 8 weeks.
Measured: 8 weeks.
Secondary outcomes (7)
Radiological Healing
Time to complete radiological healing
Measured: 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.
Measured: 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.
Measured: Up to 24 weeks.
Time from randomisation to discharge from rehabilitation.
Completion of rehab will be assessed using Army standard measures.
Measured: 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.
Measured: 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.
Measured: 4 weekly from baseline to 16 weeks
Adverse events
As reported in accordance with CTAE Version 4.03
Measured: Up to 28 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2019
- Study start23 Dec 2019
- Primary completionJun 2022 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stress FractureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Defence, United Kingdom, Darlington Memorial Hospital, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
- Responsible party
- Sponsor
- Investigators
- William Fraser, Dr, Principal investigator, Norwich Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04196855
- Sponsor's protocol ID
- 19/HRA/6011
- Acronym
- RETURN
- Status last verified
- Dec 2019
- First submitted
- 5 Dec 2019
- Last updated
- 4 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 34461961
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Teriparatide in Stress Fracture Healing
- ClinicalTrials.gov ID
- NCT04196855
- Acronym / sponsor ID
- RETURN / 19/HRA/6011
- Conditions
- Stress Fracture, Parathyroid Hormone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 136 participants (estimated)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Collaborators
- Ministry of Defence, United Kingdom, Darlington Memorial Hospital, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
- Study start
- 23 Dec 2019 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 12 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention - Teriparatide Treatment | Experimental | Drug: TeriparatideTeriparatide 20ug/day from confirmation of stress fracture for 16 weeks, with the potential to extend to 24 weeks if required. |
| Control - Standard Care | No intervention | –Standard rehabilitation care with additional monitoring to assess healing. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TeriparatideAlso: TerossaTerrosa 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. | Drug | Intervention - Teriparatide Treatment |
Primary outcome
Radiological healing.
Time frame: 8 weeks.
Radiological healing by 2 Grades or more, or to grade zero at 8 weeks.
7 secondary outcomes
Radiological Healing
Time frame: 8, 10, 12, 14, 16, 20, 24 weeks
Time from randomisation to assessed as 'Clinically Healed'.
Time frame: Twice weekly from date of radiologically healed stress fracture reported on MRI scan up to 24 weeks
Time to 'Healing' as a composite assessment.
Time frame: Up to 24 weeks.
Time from randomisation to discharge from rehabilitation.
Time frame: Up to 24 weeks
Pain symptoms on a visual analogue pain scale.
Time frame: 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
Time frame: 4 weekly from baseline to 16 weeks
Adverse events
Time frame: Up to 28 weeks.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Derived from this study: PubMed 34461961Carswell 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Carswell, Dr contact
William Fraser, Dr principal investigator
Norwich Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Teriparatide in people with Stress Fracture and Parathyroid Hormone, run by University of East Anglia at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Katharine Law (+44 (0)1603 591222, katharine.law@uea.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiological healing. (time frame: 8 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04196855, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.