Physiotherapy, Nutritional Supplement and Anabolic Steroids in Rehabilitation of Patients With Hip Fracture.

Study Overview
=================
Brief Summary
-----------------
This pilot trial investigates the preliminary effect and safety of a 12 week multi-modal intervention initiated during admission in the acute ward after hip fracture surgery. The intervention under investigation is a combination therapy consisting of physiotherapy, protein-rich nutritional supplement and nandrolone decanoate (Deca-Durabolin) supplement. The investigators expect the combination therapy to be a preliminary effective and safe treatment in elderly patients with hip fracture and that this combination therapy intervention program is more efficacious in improving muscle strength, and physical function 14 weeks after hip fracture surgery, compared to physiotherapy, protein-rich nutritional supplement plus placebo.

Official Title
-----------------
Preliminary Effect and Safety of Physiotherapy With Strength Training and Protein-rich Nutritional Supplement in Combination With Anabolic Steroids in Cross-continuum Rehabilitation of Patients With Hip Fracture - a Randomized Controlled Pilot Trial. (The HIP-SAP Trial)

Conditions
-----------------
Hip Fractures

Intervention / Treatment
-----------------
* Drug: Nandrolone Decanoate
* Dietary Supplement: Protein-rich nutritional supplement
* Other: Physical therapy
* Drug: Sodium Chloride 9mg/ml Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who have undergone surgery for a hip fracture at Amager-Hvidovre University Hospital and admitted at the Hip Fracture Unit at the hospital Age >=60 years Ability to speak and understand Danish and with a Danish Social Security Number Able to give written informed consent Residing at home and with an independent pre-fracture indoor walking ability (NMS≥2) Exclusion Criteria: Postoperative weight-bearing restrictions Multiple fractures Active cancer or suspected pathological fracture Patients unable/unwilling to cooperate to testing and rehabilitation Planned/elective hospitalization within the trial period. Cognitive dysfunction determined by chart review, reported by nursing staff, or observed by trained research staff (disoriented, dementia, active delirium) Uncontrolled blood pressure (systolic > 150 mmHg, or diastolic > 100 mmHg) Heart disease in the form of peri-, myo- or endocarditis. History of stroke with motor disability. Heart failure (NYHA class III and IV) Evidence of kidney failure or renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2 or serum creatinine >200μmol/L) Abnormal liver function tests (alanine aminotransferase, γ-glutamyltransferase, bilirubin, or alkaline phosphatase >2 times the upper limit of normal) or history of hepatic tumor. Elevated hematocrit ≥ 50% History of breast or prostate cancer Abnormally elevated serum PSA assesed at the 3 week control corresponding to PSA < 4.0 µg/L (60-70 years), PSA < 5.0 µg/L (>70 years). Allergic to any ingredient in the Deca-Durabolin solution (Nandrolone, benzyl alcohol, arachis oil (peanut-oil) and allergy to peanuts or soya) or milk protein allergy (related to the nutritional drink).

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nandrolone Decanoate<br>Physical therapy with strength training, protein-rich nutritional supplement plus Nandrolone decanoate. | Drug: Nandrolone Decanoate<br>* Injections every 3 weeks, last injection at week 12. Women 50 mg, men with total testosterone ≥ 11 nmol/l will receive 100 mg, and men with total testosterone < 11 nmol/l will receive a dose of 200 mg.<br>* Other names: anabolic steroid;Dietary Supplement: Protein-rich nutritional supplement<br>* The protein-rich nutritional supplement is a liquid containing 18 g milk-based protein pr bottle. Patients will receive a minimum of 1.35 g/kg bodyweight/day); which means that most patients will receive 2 bottles per day for 12 weeks.<br>* Other names: Nestle Resource fiber 2.0;Other: Physical therapy<br>* The physical therapy intervention will include progressive strength training initiated daily on weekdays during hospitalization and continued twice per week in the outpatient rehabilitation program in the municipality (treatment as usual but with strength training as an obligatory component) for a total intervention period of 12 weeks from time of inclusion.<br>* Other names: Physiotherapy;|
| Placebo Comparator: Placebo (Sodium Chloride)<br>Physical therapy with strength training, protein-rich nutritional supplement plus placebo. | Dietary Supplement: Protein-rich nutritional supplement<br>* The protein-rich nutritional supplement is a liquid containing 18 g milk-based protein pr bottle. Patients will receive a minimum of 1.35 g/kg bodyweight/day); which means that most patients will receive 2 bottles per day for 12 weeks.<br>* Other names: Nestle Resource fiber 2.0;Other: Physical therapy<br>* The physical therapy intervention will include progressive strength training initiated daily on weekdays during hospitalization and continued twice per week in the outpatient rehabilitation program in the municipality (treatment as usual but with strength training as an obligatory component) for a total intervention period of 12 weeks from time of inclusion.<br>* Other names: Physiotherapy;Drug: Sodium Chloride 9mg/ml Injection<br>* Placebo injection of 1 ml Sodium Chloride<br>* Other names: Saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximal isometric knee-extension strength (Nm/Kg) in the fractured limb. | Measured using a belt fixed handheld dynamometer. | Baseline and 14 weeks after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal isometric knee-extension strength (Nm/Kg) in the fractured limb in % of the non-fractured limb | Measured using a belt fixed handheld dynamometer. | Baseline and 14 weeks after inclusion | 
| Maximal isometric knee-extension strength (Nm/Kg) in the non-fractured limb. | Measured using a belt fixed handheld dynamometer. | Baseline and 14 weeks after inclusion. | 
| Hand-grip strength in the dominant hand. | Measured using a handheld dynamometer, expressed in kg. | Baseline and 14 weeks after inclusion. | 
| Bone mineral density (BMD) | Registration of total body, total hip, femoral neck, lumbar spine. Assessed by Dual-energy X-ray absorptiometry (DEXA), expressed in g/cm2. Further the T-score is registered. The DEXA is conducted in accordance with the department's standard procedures. | Baseline and 14 weeks after inclusion. | 
| Lean body mass (LBM) | Registration of total body, legs bilaterally, arms bilaterally. Assessed by DEXA and expressed in kg. | Baseline and 14 weeks after inclusion. | 
| Fat mass | Total body. Assessed by DEXA and expressed in kg. | Baseline and 14 weeks after inclusion. | 
| Nutrition screening using the Mini Nutritional Assessment Short Form (MNA-SF). | Total score from 0-14 points, high scores indicating better nutritional status | Baseline (prefracture) and 14 weeks after inclusion. | 
| Gait speed will be assessed using the 10 meter walk test (10mWT) | The results reported in meters walked per second (m/s). | Baseline and 14 weeks after inclusion. | 
| Timed up and go test (TUG) | Performed using a 4 wheeled rollator and measured in seconds. The patient has to rise from a chair, walk 3 meters, turnaround, walk back and sit down. | Baseline and 14 weeks after inclusion. | 
| The de Mortons Mobility Index (DEMMI) | Measures mobility and consists of 15 mobility items ranging from mobility in bed to dynamic balance. The test results in a total score from 0 to 100 with 100 representing the highest level of mobility. | Baseline and 14 weeks after inclusion. | 
| Upright time | Assessed by using a body-worn accelerometer-based activity monitor (ActivePAL). The monitor will be attached to the thigh. The patient will wear the monitor for 7 days. | Measured from the time of the control week 12 and one week ahead. | 
| Functional level is assessed by the New Mobility Score (NMS). | The patients are interviewed about walking ability indoor, outdoor and when shopping. the week prior to hospital admission. The total score range from 0 to 9. A Higher score indicating higher independence. | Baseline (prefracture) and 3/6/9/12/14 weeks after inclusion. | 
| The EQ-5D-3L is used for assessing health related quality of life. | It is administered via interview. | Baseline (prefracture) and 14 weeks after inclusion | 
| Hip fracture related pain at rest and during outcome assessment | It is evaluated by Verbal Ranking Scale (VRS). The patient expresses pain levels on a verbal scale from 0-4, higher score indicating higher pain levels. | Baseline and 3/6/9/12/14 weeks after inclusion. | 
| Global Rating of Change Scale | Assessment of patient perceived change in walking ability during the trial period. | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| The Short Falls Efficacy Scale-International (Short FES-I) | Measures the patient's fear of falling (Score 7-28, higher scores indicating a higher fear of falling). It is administered as an interview. | Baseline and 14 weeks after inclusion. | 
| Fatigue is assessed using the Short Form (36) Health Survey (SF36) vitality subscale. | The scale consists of 4 items related to fatigue/energy. Score range from 0-100 points; high score defines a more favorable health state. Administered as an interview. | Baseline (prefracture), and 3/6/9/12/14 weeks after inclusion. | 
| Depression is assessed using the Geriatric Depression Scale (GDS-15) | Administered as an interview. Score range 0-15. | Baseline (prefracture) and 14 weeks after inclusion. | 
| Re-admissions | Assessed through the medical journal/interviews. | 14 weeks after inclusion. | 
| Residential status (including home care) | Change in residential status and home care (help provided in the patients home). Assessed through the medical journal/interviews. | Baseline (prefracture) and 14 weeks after inclusion. | 
| Mortality | Assessed through the medical journal/Danish civil register. | 14 weeks after inclusion. | 
| Falls | Number of falls. Assessed through interviews | Assessed through weekly telephone interviews and hospital visits at 3/6/9/12/14 weeks after inclusion. | 
| Total testosterone (nmol/l) | Blood test | Baseline and 14 weeks after inclusion. | 
| Luteinizing hormone (LH), IU/l | Blood test | Baseline and 14 weeks after inclusion. | 
| Follicle-stimulating hormone (FSH) IU/l | Blood test | Baseline and 14 weeks after inclusion. | 
| Sex hormone binding globulin (SHBG), nmol/l | Blood test | Baseline and 14 weeks after inclusion. | 
| Lipid profile (Total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride) mmol/l. | Blood test | Baseline and 14 weeks after inclusion. | 
| C-reactive protein (CRP), mg/l. | Blood test | Baseline and 14 weeks after inclusion. | 
| Hematocrit (B-Erythrocyte, vol.fr.) | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Hemoglobin | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Creatinine | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Carbamide | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Sodium (Na+) | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Potassium (K+) | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Calcium | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Liver tests (Albumin, Alanine aminotransferase (ALAT), γ-glutamyltransferase, Bilirubin) | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| International Normalized Ratio (INR) | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Prostate Specific Antigen (PSA) | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Glucose | Safety parameter, blood test | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Blood pressure | Safety parameter, assessed using a 'Blood pressure monitor' (mmHg). | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Facial hirsutism | Change in facial hair assessed using the 2 face-related items of Ferriman-Galway Hirsutism Score. | Baseline, and 3/6/9/12/14 weeks after inclusion. | 
| Hoarseness | Change in voice, reported by patient or observed by interviewer (no specific score available for this evaluation). | Assessed at baseline and through weekly telephone interviews and hospital visits at 3/6/9/12/14 weeks after inclusion. | 
| Other adverse events | Assessed through interview, observation | Assessed through weekly interviews and hospital visits at 3/6/9/12/14 weeks after inclusion. | 
| Edema in non-fractured leg | Change in edema assessed through interview | Assessed at baseline and through weekly interviews and hospital visits at 3/6/9/12/14 weeks after inclusion. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rehabilitation, Physiotherapy, Strength training, Anabolic steroids, Nutritional supplement