E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
DHEA depletion in trauma and hip fracture patients. |
|
E.1.1.1 | Medical condition in easily understood language |
Low hormone levels in patients who have been severely injured in accidents or have a hip fracture. |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056629 |
E.1.2 | Term | Dehydroepiandrosterone decreased |
E.1.2 | System Organ Class | 10022891 - Investigations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish a dose of supplemental Dehydroepiandrosterone (DHEA) sufficient to raise circulating DHEA levels in severely injured trauma and hip fracture patients, after up to 3 days of supplementation, to levels observed in healthy young male adults.
|
|
E.2.2 | Secondary objectives of the trial |
To review the effect of a single and multiple dose of DHEA on circulating DHEA and DHEAS levels and related hormones.
To assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles of severely injured trauma and female hip fracture patients.
To identify what route of DHEA administration is more efficient at raising DHEA levels sufficiently.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The inclusion criteria is split into trauma patients and hip fracture patient cohorts.
TRAUMA PATIENTS INCLUSION CRITERIA (males and females) - 16 - 50 years of age - Severely injured trauma patient (Injury severity score (ISS) ≥16 and ≤50) - Admitted to University Hospital Birmingham within 6 days of trauma - Anticipated to be an inpatient for the 11 day trial period
HIP FRACTURE PATIENTS INCLUSION CRITERIA (females only) - 50 years of age and older. - Female. - Neck of Femur fracture. - Admitted to University Hospital Birmingham within 6 days of fracture. - Anticipated to be an inpatient for the 11 day trial period.
|
|
E.4 | Principal exclusion criteria |
The exclusion criteria is split into trauma patients and hip fracture patient cohorts.
TRAUMA PATIENTS EXCLUSION CRITERIA 1. Ages <16 or >51 years of age. 2. ISS <16 or >50 3. Isolated brain injury. 4. Unlikely to survive the study period (11 days). 5. Previous or known hormone sensitive malignancy. 6. Known Prostatic hypertrophy (M) 7. Intake of adrenal medication prior to admission to hospital. 8. Female patients taking Hormone Replacement Therapy medication. 9. Intake of any drugs that is likely to influence the metabolism of steroids, in particular inducers and inhibitors of the drug-metabolising enzyme CYP3A4 in the last 3 months. 10. Previous documented liver failure. 11. Current malignancy with ongoing active treatment. 12. Prescribed antipsychotic medication. 13. Pregnant and/or breast-feeding females
HIP FRACTURE PATIENTS EXCLUSION CRITERIA 1. <50 years of age. 2. Unlikely to survive the study period (11 days). 3. Previous or known hormone sensitive malignancy. 4. Intake of any drugs that is likely to influence the metabolism of steroids, in particular inducers and inhibitors of the drug-metabolising enzyme CYP3A4 in the last 3 months. 5. Previous documented liver failure. 6. Current malignancy with ongoing active treatment. 7. Prescribed antipsychotic medication. 8. Pregnant and/or breast-feeding females
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
To establish a dose of supplemental Dehydroepiandrosterone (DHEA) sufficient to raise circulating DHEA levels in injured trauma and hip fracture patients, after 3 days of supplementation, to levels observed in healthy young male adults.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood samples once daily on day 7,8,9,10,11. |
|
E.5.2 | Secondary end point(s) |
To establish an optimal dose of DHEA to enhance immune function through the assessment of neutrophil function and cytokine profiles.
To assess if DHEA supplementation via sublingual administration is more effective than an oral administration of the same dose.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood samples once daily on day 7,8,9,10,11. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of trial will be the last patient last visit from the male trauma or female hip fracture groups. The female trauma group will only be recruiting until the other two patient groups are complete. This is due to low admissions of females with a traumatic injury and based on admission data it could take up to 4 years to recruit 90 patients. We envisage that this trial will take 18 months to complete recruitment. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |