Trial document




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  DRKS00007824

Trial Description

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Title

Effects of endurance exercise on incidence and severity of cognitive impairments and other therapy-related side effects in leukemia and lymphoma patients undergoing high-dose chemotherapy. A randomized controlled trial.

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

A significant number of survivors of cancer treatments report adverse effects in cognitive function during and even after medical therapy. So far studies using cognitive tests found deficits especially in the areas of concentration, mental ability and memory. Currently the presence of several factors is suspected to be influencing these deficits: amongst others the specific therapy, the specific tumor and also the age and cognitive capability as well as mental stress of the patient. Until now, there are no effective treatments to prevent these cognitive side-effects. However, elderly people and patients with neurodegenrative diseases showed improvemed results after aerobic exercise interventions in their cognitive performances. Encouraged by these findings the aim of this study therefore is to explore whether aerobic exercise is able to counter cognitive depletion caused by cancer treatments. The planned study examines patients with leukaemia and lymphoma disease shortly before a scheduled high-dose systemic chemotherapy or just after start of the therapy.
The participants are randomly assigned to one of three groups. Participants assigned to the first group receive a cycle intervention on an ergometer for 3 times per week for 15-25 minutes each additional to their usual care treatments. Participants assigned to the second group receive a low-intensity stretching and mobility training for the same amount of time auxiliary to their usual care treatments. Intensity and duration of the training sessions is adapted to the patient's current health status. Participants assigned to the third group receive the usual care with no additional treatment. Before and after therapy (approx. four to eight weeks) participants perform several tests in order to analyse the hypothesis whether endurance exercise can counter the depletion of cognitive capability of cancer patients undergoing chemical therapy. Depending on the planned therapy a follow up measurment will be carried out at the patient's readmission (approx. two to three weeks later). As part of a substudy the effect of one single training intervention (endurance training) on the well being and the congitive functioning of the participants will be measured. Additionally to the main hypothesis, various aspects, such as quality of life, fatique, infection risk, psychological exposure and immune status will be documented and analysed.

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Brief Summary in Scientific Language

Approximately 20-30% of cancer patients show cognitive impairments during and after the implemention and completion of their medical therapy (especially verbal memory and executive function). These deficits are also known as „cancer related cognitive impairments“ (CRCI) (see also Ahles & Root, 2018). 75 cancer patients with either acute leukemia or lymphome will be included in this study. Measurments will be carried out just after receiving the first chemotherapy (t0), just after the last dose of the high-dose treatment (t1) and, depending on the clinical course, in a follow-up measurment two to three weeks later (t2) measuring neuro-cognitive capability. Participants will be randomly assigned to one of three groups: the exercise group (IG), the active control group (aKG) and the passive control group (pKG). During the four to eight weeks of highly dosed chemotherapy, participants assigned to the IG perform a three times a week cycling intervention on an stationary ergometer aiming for 30 minutes of training per session. Participants assigned to the aKG perform a low-intensity stretching and mobilization training for the same amount of time. Participants assigned to the pKG receive usual care but no further treatment. The primary objective of the study is to determine whether the intervention improves or maintains cognitive decline (especially verbal memory and executive function). Data will be collected using the computer-based Wiener Test-System (WTS). Additionally, the objective measurements will be complemented by questionnaires regarding subjectivly perveived fatique, subjectivly perceived cognitive performance and psychological adverse effects at all measurement points (t0, t1, t2). In addition, the physical performance capability is tested using a step test and a dynamometer. At all measurement points an analysis of blood sample parameters is conducted.
In the context of a substudy, the effect of one single intervention on cognitive performance will be examined. For this purpose, tests measuring the colour and word interference, the ability of retrospection and the current well-being are carried out before and immediately after the intervention session (according to the randomization).

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Organizational Data

  •   DRKS00007824
  •   2016/01/26
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  •   yes
  •   Approved
  •   15-161, Ethik-Kommission der Medizinischen Fakultät der Universität zu Köln
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Secondary IDs

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Health Condition or Problem studied

  •   C92.0 -  Acute myeloblastic leukaemia [AML]
  •   C91.0 -  Acute lymphoblastic leukaemia [ALL]
  •   C91.8 -  Mature B-cell leukaemia Burkitt-type
  •   C83.5 -  Lymphoblastic (diffuse) lymphoma
  •   C83.7 -  Burkitt lymphoma
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Interventions/Observational Groups

  •   The intervention group recieves a cycle intervention on an ergometer 3x/week for 15-25 minutes at the date of recruiting (during their ca. 4-weeks of highly dosed chemotherapy). The ergometer intervention will be administered at 65-85 % of the patient`s individual maximal heart rate. Contraindications for participation in the study are acute infections, fever, dizziness, hemoglobin levels below 8g/dl, thrombocytes levels below 10.000/μl and/or systolic blood pressure over 160 mmHg. The interventions takes place in the hospital wards of the university hospital cologne. The performance of each unit is authorized by the consent of the treating doctor. This is estimated for every individual case.
    In case of contraindications the training session is replaced by a relaxation session if possible.
  •   Analogous to the intervention group, the active control group performs a 3x/week for 15-25 minutes a stretching and mobilization training. Contraindications for participation in this training are acute infections, fever, dizziness, hemoglobin levels below 8g/dl, thrombocytes levels below 10.000/μl and/or systolic blood pressure over 160 mmHg. The interventions takes place in the hospital wards of the university hospital cologne. The performance of each unit is authorized by the consent of the treating doctor. This is estimated for every individual case.
    In case of contraindications the training session is replaced by a relaxation session if possible.
  •   Patients assigned to passive control group receive usual care.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   caregiver, data analyst
  •   Active control (effective treament of control group), Control group receives no treatment
  •   Supportive care
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

The following tests are executed to analyse the cognitive performance at all points of measurment:
a) For examining inhibition performance the response inhibition test (INHIB) was applied. The INHIB is a typical task from the Go/No-go paradigm. Therefore the participants are presented to 202 triangle in grey (Go-stimuli) and 48 circle in grey (No-go-stimuli) in a random order on the computer screen and they are instructed to respond as quickly as possible to Go-stimuli by pushing a button on a special keyboard and to show no reaction at all to No-go-stimuli. Every single stimuli will be presented for 200 milliseconds. There is a time lag of one second between the stimuli. For this time, the monitore stays black. The main variable the system counts the number of wrong executions on Go-Stimuli and the mean motor time of these stimuli. This is known as a valid measurement of response inhibiton (see also Royall, Lauterbach, Cummings, Reeve, Rummans, Kaufer et al., 2002).

b) Trail-Making-Test Langensteibacher version: The TMT is a test of visuomotor speed (part A) and executive function (part B). In TMT-A, participants are asked to draw a line connection cicled numbers from 1 to 25 as fast and accurately as possible. The score is the time required to connect the circles. TMT-A measures selective attention (see also Daamen & Raab, 2012; Rüsseler, 2010). In TMT-B, participants are asked to draw a line connection ascending, alternating, numbers and letters (1-A-2-B-3-C, etc.). The score is the time required to complete the task. TMT-B measures reactive kognitive flexibility and set shifting (see Daamen & Raab, 2012). If participants cannot complete the task in 300 seconds, the test is terminated.


c) The Hopkins Verbal Learning Test --> This procedure examines verbal learning. Participants are presented a list of 12 nouns belonging to three different semantic categories. There are three learning trials and after each participants recall as many words as they remember. 20-25 minutes after the last training trial delayed recall is tested. Subsequently a recognition trial is executed during which participants are presented to 24 words including initial 12 and additional 12 nouns. During recognition trial participants are supposed to identify those words belonging to the initially learned list.

d) The Regensburger verbal fluency test --> This test is the most commonly used test in German for examination of participants` verbal fluency. It comprises a test form of lexical and semantical verbal fluency. The former means producing as many words beginning with a specific letter while the letter means producing as many words from a defined semantic category.

e) Dresden Spatial Navigations Task --> The Dresden Spatial Navigation Task (DSNT), also known as Water-Maze-Test, includes the ability of spatial navigation in a formerly unknown and complex environment. The paradigm is the Morris water labyrinth adapted for humans, a validated test for lab animals applied for more than 30 years in fundamental research. The Water-Maze-Test has been designed for computer simulation thus can be used on every advanced Windows computer including 3D graphics card. Completing the DSNT exercise and given that the target is invisible, the participants are repeatedly asked to find a platform under water in a virtual circular swimming pool sourrounded by walls. Participants navigate with the forward and backwards arrow keys on the keyboard. Outside and above the swimming pool there are colored geometric figures as orientation points. Once having reached the target or once the task could not be completed in a given time, participants will be automatically pulled towards the invisible target in order to learn how to reach the target by means of the geometric figures. Afterwards the participant tries to find the target again up to 8 times in total from various areas of the swimming pool. During the learning process the human brain develops a neuronal representation of the environment and the available geometric figures, which is called cognitive map enabling a precise approach towards a learned target from any given starting point. This is localised in the Hippocampus. The Hippocampus is a phylogeneticly old brain structure that is significantly involved in the development of human memory. Also, the Hippocampus plays a decisive role in spatial and episodic brain and provides saving of sensoric context into relational structures, which is then called cognitive map. With this map, humans are able to flexibly navigate their behaviour based on previously learned activities. Both exercise and key concepts are being explained to participants via the screen and by the test leader supervising that the few basic rules are met. The entire exercise has an economic time frame of 20-25 minutes.

f) The Der Rey–Osterrieth Complex Figure Test (ROCF) --> The ROCF is a neuropsychological testing procedure capturing one`s ability of visuospatial construction and memory.

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Secondary Outcome

Following dependent variable are recordet at t0, t1 and t2:
Subjective cognitive performance --> Functional Assessment of Cancer Therapy - Cognitive Function)

The quality of life of patients --> EORTC QLQ-C30 questionnaires

Psychological stress of patients --> Hospital Anxiety and Depression Scale

Patients` fatigue --> Multidimensional Fatigue Inventory - 20 Items questionnaire

Level of activity: körperliche Aktivitätsskala

Perfromance Status --> Classification of the Eastern Cooperative Oncology Group (ECOG Performance Status)

Determination of immune statues and periphere neurotrophic factors of patients --> analyse relevant blood parameters

Physical performance of patients --> spiroergometric performance and hand dynamomter

Relief of sleep disturbance of the patients --> Pittsburgh sleep quality index

Mesurment of acute effects:
Color/word interference (Stroop-Test), metal state (MDBF), verbal memory (HVLT-R form 5&6)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2016/05/03
  •   75
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- A Diagnosis of an acute leukemia

- Approach induction therapy or high dose chemotherapie (for example B-ALL-protocol, GMALL-protocol) or protocols with the therapy aim of a stem cell transplantation (for example DHAP-Induction, S-HAM)

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Exclusion Criteria

- Age <18 years

- Comorbidities which prohibit physical activity (coronary heart disease, heart failure NYHA>3, orthopedic illness, cerebral spasm, psychological illness)

- A planned surgery

- Metastasis of CNS

- Other medical reasons not to participate in the study

- Cognitive impairment (dementia, MS, apoplex, traumatic brain injury, brain tumor

- Lack of willingness for data tob e saved and further processed

- outpatient therapy, which does not allow training on a regulare basis

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Addresses

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    • Prof. Dr. Wilhelm Bloch Institut für Kreislaufforschung und SportmedizinAbteilung für molekulare und zelluläre SportmedizinDeutsche Sporthochschule Köln
    • Mr.  Dr. Dr.  Philipp  Zimmer 
    • Am Sportpark Müngersdorf 6
    • 50933  Köln
    • Germany
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    • Dr. med. Thomas Elter Facharzt für Innere Medizin, Hämatologie und Onkologie (MVZ)
    • Mr.  Dr. med  Thomas  Elter 
    • Köln
    • Germany
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    • Institut für Kreislaufforschung und SportmedizinAbteilung für molekulare und zelluläre SportmedizinDeutsche Sporthochschule Köln
    • Ms.  M. Sc.  Anja  Großek 
    • Am Sportpark Müngersdorf 6
    • 50933  Köln
    • Germany
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    • Institut für Kreislaufforschung und SportmedizinAbteilung für molekulare und zelluläre SportmedizinDeutsche Sporthochschule Köln
    • Mr.  MSc.  Florian  Wolf 
    • Am Sportpark Müngersdorf 6
    • 50933  Köln
    • Germany
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Sources of Monetary or Material Support

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    • Institut für Kreislaufforschung und SportmedizinAbteilung für molekulare und zelluläre SportmedizinDeutsche Sporthochschule Köln
    • Mr.  Prof. Dr.  Wilhelm  Bloch 
    • Am Sportpark Müngersdorf 6
    • 50933  Köln
    • Germany
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    • Marga und Walter Boll-Stiftung
    • 50170  Kerpen
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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