Physiotherapy, Nutritional Supplement and Anabolic Steroids in Rehabilitation of Patients With Hip Fracture. (HIP-SAP)

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)

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.

Study Overview

• Status: Completed
• Conditions: Hip Fractures
• Intervention / Treatment: Drug: Nandrolone Decanoate; Dietary supplement: Protein-rich nutritional supplement; Other: Physical therapy; Drug: Sodium Chloride 9mg/ml Injection

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nandrolone Decanoate; Physical therapy with strength training, protein-rich nutritional supplement plus Nandrolone decanoate.	Drug: Nandrolone Decanoate; 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.; Other Names: Deca-durabolin; anabolic steroid; Dietary supplement: Protein-rich nutritional supplement; 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.; Other Names: Nestle Resource fiber 2.0; Other: Physical therapy; 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.; Other Names: Physiotherapy
Placebo Comparator: Placebo (Sodium Chloride); Physical therapy with strength training, protein-rich nutritional supplement plus placebo.	Dietary supplement: Protein-rich nutritional supplement; 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.; Other Names: Nestle Resource fiber 2.0; Other: Physical therapy; 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.; Other Names: Physiotherapy; Drug: Sodium Chloride 9mg/ml Injection; Placebo injection of 1 ml Sodium Chloride; 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.

Collaborators and Investigators

• Sponsor: Morten Tange Kristensen PT, PhD
• Investigators: Study Director: Morten T Kristensen, PT, PhD, Department of Occupational and Physical Therapy and Department of Orthopedic Surgery, Amager-Hvidovre University Hospital

Publications and helpful links

General Publications

• Hulsbaek S, Bandholm T, Ban I, Foss NB, Jensen JB, Kehlet H, Kristensen MT. Feasibility and preliminary effect of anabolic steroids in addition to strength training and nutritional supplement in rehabilitation of patients with hip fracture: a randomized controlled pilot trial (HIP-SAP1 trial). BMC Geriatr. 2021 May 20;21(1):323. doi: 10.1186/s12877-021-02273-z.
• Hulsbaek S, Ban I, Aasvang TK, Jensen JB, Kehlet H, Foss NB, Bandholm T, Kristensen MT. Preliminary effect and feasibility of physiotherapy with strength training and protein-rich nutritional supplement in combination with anabolic steroids in cross-continuum rehabilitation of patients with hip fracture: protocol for a blinded randomized controlled pilot trial (HIP-SAP1 trial). Trials. 2019 Dec 23;20(1):763. doi: 10.1186/s13063-019-3845-y.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Actual): May 20, 2020
• Study Completion (Actual): June 3, 2020

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 4, 2018

Study Record Updates

• Last Update Posted (Actual): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Rehabilitation; Physiotherapy; Strength training; Nutritional supplement; Anabolic steroids
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bone Density Conservation Agents; Androgens; Anabolic Agents; Nandrolone; Nandrolone Decanoate; Nandrolone phenpropionate
• Other Study ID Numbers: HvidovreUH-HIP-SAP-1; 2017-001543-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No