Strength Training as Prevention and Treatment of Late Effects in Long-term Survivors of Pediatric HSCT.

Study Overview
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Brief Summary
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Today the overall survival of childhood cancers has increased to above 85%. This increase is partially caused by treatment with bone marrow transplantation. A bone marrow transplantation is an efficient treatment against high-risk leukemia, as well as other life-threatening immunological and hematological diseases. However, it is unfortunately also related to the risk of developing a long series of late effects during early adulthood, such as low muscle mass, cardiovascular disease and diabetes. Conditions known from the older generations of the general population and also conditions highly related to lifestyle factors in the general population. In the group of survivors after bone marrow transplantation, the cause for these late effects is not fully understood, as the same close association to lifestyle factors as seen in the general population, is not present in this group. Multiple studies have examined the possible causes, and it have been shown that certain elements of a bone marrow transplantation, ie. total body irradiation, are associated with the risk of developing late effects. As the cause is not fully understood, it is not known whether the treatment and preventive strategies, that would be applied in the general population for these conditions, are effective in this group. Therefore, in this study the investigators aim at examining the effect of a strength training intervention on the development of the aforementioned late effects to treatment with bone marrow transplantation during childhood. The investigators will invite a group of persons, transplanted during childhood, as well as an age- and sex-matched control group to participate in the study. Both groups will go through a 16-week strength training intervention, and a thorough health examination before and after the intervention, to assess metabolic status and body composition. If the investigators find a positive effect of strength training on muscle mass and risk factors for developing cardiovascular disease and diabetes in persons, treated with bone marrow transplantation during childhood, it will support the implementation of structured training programs in the follow-up of these patients. Thereby hopefully contributing to an increased quality of life, as well as an increased life expectancy in the group of survivors after bone marrow transplantation during childhood.

Official Title
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Strength Training as Prevention and Treatment of Late Effects in Long-term Survivors of Pediatric HSCT.

Conditions
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Late Effect, Stem Cell Transplant, Metabolic Syndrome, Cardiovascular Diseases

Intervention / Treatment
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* Other: Strength training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living in Copenhagen, Denmark or surrounding area - making it possible to engage in strength training 3 times a week at Bispebjerg Hospital, Copenhagen, Denmark. ≥ 18 years old Exclusion Criteria: Illness or physical handicap making it impossible to participate in the training intervention Pregnancy Not Danish or English speaking Anemia Already performing regular structured physical training Strict vegan or vegetarian diet Illness or ongoing treatment that hinders study examinations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: The same interventon will be applied to two groups, a group of previously recipients of bone marrow transplantation, and a group of age- and sex-matched controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Strength training<br>In this arm participants will go through the Strength training intervention. | Other: Strength training<br>* The interventon consist of 3 weekly, supervised group sessions for 4 months (16 weeks). The sessions consist of progressive full body strength training with a primary focus on lower extremity muscle strength. The leg exercises are leg press, knee extension and leg curl. In addition, participants will perform two upper body exercises. Physical assessment will take place immediately and monthly until 4 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cross sectional area of m. quadricpes femoris. | Muscle mass as measured by cross sectional area of m. quadriceps femoris at midthigh level, on an MRI scan. | 1 week pre intervention | 
| Changes in cross sectional area of m. quadricpes femoris. | Muscle mass as measured by cross sectional area of m. quadriceps femoris at midthigh level, on an MRI scan. | 1 week post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in components of the Metabolic Syndrome: Waist circumference | Waist circumference will be measured at the level of the superior border of the iliac crest, at the end of a normal expiration with a tape measure to the nearest 0.1 cm, as suggested by The US National Cholesterol Education Programme. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week pre intervention | 
| Changes in components of the Metabolic Syndrome: Waist circumference | Waist circumference will be measured at the level of the superior border of the iliac crest, at the end of a normal expiration with a tape measure to the nearest 0.1 cm, as suggested by The US National Cholesterol Education Programme. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week post intervention | 
| Changes in components of the Metabolic Syndrome: Triglycerides | Blood samples will be drawn from a cannual placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week pre intervention | 
| Changes in components of the Metabolic Syndrome: Triglycerides | Blood samples will be drawn from a cannual placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week post intervention | 
| Changes in components of the Metabolic Syndrome: HDL-cholesterol | Blood samples will be drawn from a cannual placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week pre intervention | 
| Changes in components of the Metabolic Syndrome: HDL-cholesterol | Blood samples will be drawn from a cannual placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week post intervention | 
| Changes in components of the Metabolic Syndrome: Fasting glucose | Blood samples will be drawn from a cannual placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week pre intervention | 
| Changes in components of the Metabolic Syndrome: Fasting glucose | Blood samples will be drawn from a cannual placed in an antecubital vein or a dorsal vein in the hand. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week post intervention | 
| Changes in components of the Metabolic Syndrome: Blood pressure | Blood pressure will be measured on the upper arm while sitting in the suppine position, after 10 minutes of rest, with an automated blood pressure monitor. Blood pressure will be measured three times, or untill there is less than 10 mmHg difference between measurements. The final blood pressure will be a mean of the two last measurements. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week pre intervention | 
| Changes in components of the Metabolic Syndrome: Blood pressure | Blood pressure will be measured on the upper arm while sitting in the suppine position, after 10 minutes of rest, with an automated blood pressure monitor. Blood pressure will be measured three times, or untill there is less than 10 mmHg difference between measurements. The final blood pressure will be a mean of the two last measurements. Patients will be classified according to The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) definition of the Metabolic Syndrome. We will report changes in the number of components fulfilled. | 1 week post intervention | 
| Hip circumference | Measurement of hip circumference at the widest part of the buttocks with a tape measure, to the nearest 0.1 cm. | 1 week pre intervention | 
| Hip circumference | Measurement of hip circumference at the widest part of the buttocks with a tape measure, to the nearest 0.1 cm. | 1 week post intervention | 
| Urine sample - microalbuminurea | A urine sample for analyses of microalbuminurea in mg/L. | 1 week pre intervention | 
| Urine sample - microalbuminurea | A urine sample for analyses of microalbuminurea in mg/L. | 1 week post intervention | 
| Muscle strength of quadriceps femoris | Rate of force development, maximal isometric and dynamic force capacity measured by KinCom Dynamometer | 1 week pre intervention | 
| Muscle strength of quadriceps femoris | Rate of force development, maximal isometric and dynamic force capacity measured by KinCom Dynamometer | 1 week post intervention | 
| Handgrip strength | Handgrip strength measured with handheld Dynamometer | 1 week pre intervention | 
| Handgrip strength | Handgrip strength measured with handheld Dynamometer | 1 week post intervention | 
| Muscle performance: Timed-up-and-go | Timed-up-and-go test: The participant sits on a chair, that allow the participant to flex the leg at a 90 degree angle, with the back against the chair and arms on the knees. From this position the participant stands up straight and walk 3 m, turns around and go back to the chair and sit down as fast as possible, time in seconds is the outcome. The lowest score of three consecutive tries will be used in the analysis. | 1 week pre intervention | 
| Muscle performance: Timed-up-and-go | Timed-up-and-go test: The participant sits on a chair, that allow the participant to flex the leg at a 90 degree angle, with the back against the chair and arms on the knees. From this position the participant stands up straight and walk 3 m, turns around and go back to the chair and sit down as fast as possible, time in seconds is the outcome. The lowest score of three consecutive tries will be used in the analysis. | 1 week post intervention | 
| Muscle performance: Sit-to-stand 30 sec. | Sit-to-Stand 30 sec: The participant sits on a chair allowing the participant to flex the legs at a 90 degree angle. The participant is instructed to stand up straight, and return to sitting, as many times as possible in 30 sec. The arms should be crossed in front of the body or hanging by the side. Number of repititions is the outcome. | 1 week pre intervention | 
| Muscle performance: Sit-to-stand 30 sec. | Sit-to-Stand 30 sec: The participant sits on a chair allowing the participant to flex the legs at a 90 degree angle. The participant is instructed to stand up straight, and return to sitting, as many times as possible in 30 sec. The arms should be crossed in front of the body or hanging by the side. Number of repititions is the outcome. | 1 week post intervention | 
| Muscle performance: Sit-to-stand 60 sec. | Sit-to-Stand 60 sec: The participant sits on a chair allowing the participant to flex the legs at a 90 degree angle. The participant is instructed to stand up straight, and return to sitting, as many times as possible in 60 sec. The arms should be crossed in front of the body or hanging by the side. Number of repititions is the outcome. | 1 week pre intervention | 
| Muscle performance: Sit-to-stand 60 sec. | Sit-to-Stand 60 sec: The participant sits on a chair allowing the participant to flex the legs at a 90 degree angle. The participant is instructed to stand up straight, and return to sitting, as many times as possible in 60 sec. The arms should be crossed in front of the body or hanging by the side. Number of repititions is the outcome. | 1 week post intervention | 
| Cardiorespiratory fitness: 6 minute walk test | 6 min. walk test: The participant walks as far as possible on a 15 m lane in 6 min. Distance in meters is the outcome. | 1 week pre intervention | 
| Cardiorespiratory fitness: 6 minute walk test | 6 min. walk test: The participant walks as far as possible on a 15 m lane in 6 min. Distance in meters is the outcome. | 1 week post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Strength training, Resistance training