Healthy individuals with stress fractures. MedDRA version: 20.1 Level: PT Classification code 10042212 Term: Stress fracture System Organ Class: 10022117 - Injury, poisoning and procedural complications MedDRA version: 20.1 Level: PT Classification code 10042212 Term: Stress fracture System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Trade Name: Terrosa
Product Name: Terrosa
Pharmaceutical Form: Suspension for injection in cartridge
INN or Proposed INN: Teriparatide
Concentration unit: µg/ml microgram(s)/millilitre
Concentration t
Sponsors
Norfolk and Norwich University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed informed consent and able to comply with protocol; 2) Aged 18 to 40 years; 3) Lower limb stress fracture, confirmed by MRI scan; 4) Undergoing phase 1 or 2 training within an Army training establishment; 5) Baseline blood tests within reference range (see table 3 for more details). Minor abnormalities will be assessed by the PI. Patients will still be eligible if these are felt to be of no clinical importance and this decision is documented by the PI; 6) Participant is able to adhere to visit requirements. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 136 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1) Hypersensitivity to the active Parathyroid Hormone substance or any of the excipients listed in the SPC. 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 birth control method which may be considered as “highly effective”, 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. **As per the CTFG guidance and for the purposes of this trial, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12-months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. In accordance with CTFG guidance, methods that can achieve a failure rate of less than 1% per year when used consistently and correctly, are considered as “highly effective” birth control methods. Such methods include: - Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (either oral, intravaginal or transdermal); - Progestogen-only hormonal contraception associated with inhibition of ovulation (either oral, injectable or implantable); - Intrauterine device (IUD); - Intrauterine hormone-releasing system (IUS); - Bilateral tubal occlusion; - Vasectomised partner; - Sexual abstinence. (Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated for the duration of the participant’s treatment period during the trial and the preferred and usual lifestyle of the participant.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary outcome for the trial will be the improvement in radiological healing by 2 grades or more, ‘or complete healing’, indicated by a grade of zero, at 8 weeks post-randomisation. Assessed by MRI using the modified Fredericson Stress Fracture Grading System High-Signal Short TI Inversion Recovery (STIR) Image. ;Secondary Objective: The secondary outcomes will be as follows: -Does PTH reduce the time to radiological healing (as assessed by MRI scanning at weeks 8, 10, 12, 14 and 16 (five in total)). * Where participants are still assessed as not clinically healed, the treatment phase will be extended to 6-months, necessitating 2 further scans at weeks 20 and 24. These participants will therefore undergo a maximum of 7 MRI scans in total. This may be extended to 7 scans in total however, -Proportion assessed as ‘Clinically Healed’. Clinical assessments will be carried out twice a week at ITC(C) following an MRI grade 0 by a local researcher. - Healing as a composite assessment of healing by MRI and clinical assessment. - Time from randomisation to discharge from rehabilitation. Completion of rehabilitation will be assessed using Army standard measures. - Pain symptoms using a visual analogue pain scale in a diary to be completed weekly and analysed as a change from baseline to 16 weeks (24 weeks in an unh;Primary end point(s): The primary outcome for the trial will be the improvement in radiological healing by 2 grades or more, ‘or complete healing’, indicated by a grade of zero, at 8 weeks post-randomisation (assessed using the modified Fredericson Stress Fracture Grading System by MRI and High-Signal Short TI Inversion Recovery (STIR) Image). ;Timepoint(s) of evaluation of this end point: MRI scans will be performed at weeks 8, 10, 12, 14 and 16 (5 in total). Radiological healing will be assessed using the modified Fredericson Stress Fracture Grading System by MRI and High-Signal Short TI Inversion Recovery (STIR) Image. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes will be as follows: • Proportion assessed as ‘Clinically Healed’. Clinical assessments will be carried out twice a week at ITC(C) following an MRI grade 0 by a blinded researcher. • Healing as a composite assessment of healing by MRI and clinical assessment. • Time from randomisation to discharge from rehabilitation. Completion of rehabilitation will be assessed using Army standard measures. • Pain symptoms using a visual analogue pain scale in a diary to be completed weekly and analysed as a change from baseline to 16 weeks (24 weeks in an unhealed fracture). • Quality of life (assessed by SF36 Questionnaire) and any other appropriate questionnaires used by the army to assess readiness to return to training. • Adverse Events including the number and severity of Adverse Reactions. MRI scans will be performed at weeks 8, 10, 12, 14 and 16 (5 in total). Radiological healing will be assessed by MRI using the modified Fredericson Stress Fracture Grading System and High-Signal Short TI Inversion Recovery (STIR) Image. The scale proposed by Beck et al. will be used to assess clinical healing. Further Exploratory outcomes are as follows: • Biochemical responses to treatment (assessed in blood and urine samples) at weeks 4, 8, 12 and 16. This will be extended to weeks 20 and 24 for participants that remain in the trial. Laboratory technicians analysing the samples will be blinded. • Changes in bone density and micro architecture, assessed by DXA at the hip and spine between the point of randomisation and week 16, and HRpQCT at the distal radius (non-dominant arm) and distal tibia (non-fractured limb) between the point of randomisation and weeks 16 or 24. The images will be processed by by a blinded, experienced researcher. • Differences in the physical activity levels between the treatment and control arm from the point of randomisationto week 16, or week 24 in the case of an unhealed fracture. A wrist-mounted, tri-axial | — |
Countries
United Kingdom
Contacts
Public ContactAnn Marie Swart
Norwich Clinical Trials Unit
Outcome results
None listed