Refractory EpilepsyEpilepsyNCT03570489
Randomized Controlled Trial on Cardiovascular Exercise in Uncontrolled Epilepsy:
A study testing Exercise and Relaxation in people with Refractory Epilepsy, run by Vastra Gotaland Region at 1 site in Sweden.
Trial summary
This is an open-label randomized controlled tria testing if an improvement in cardiovascular fitness can improve quality of Life and reduce seizure frequency in patients with refractory epilepsy.. Before the intervention each subject will undergo an evaluation of baseline cardiovascular fitness. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- Exercise and Relaxation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteSweden
- Study dates
- 30 Nov 2018to 6 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years to 65 years
- An established diagnosis of focal epilepsy
- A frequency of at least 3 focal seizures (including focal to bilateral tonic-clonic) during a 4 week-prospective baseline, despite ongoing treatment with one to 4 AEDs
- Stable AED treatment for at least 4 weeks, and no expected need to modify current AED treatment over the subsequent 6 months.
- Capability to follow instructions (or has a caretaker who will help) and keep a seizure calendar
- Ability to understand the purpose, procedures and potential risks and benefits associated with participation in the study;
- Willingness to give freely written informed consent
Who cannot join
- Any associated condition contraindicating non-competitive physical exercise
- Patients already engaged in regular daily physical exercise program;
- A history of seizures induced by exercise
- A history of psychogenic non-epileptic seizures
- Pregnancy or puerperium
- Alcohol or substance abuse
- Any condition (for example, an unstable or progressive medical condition) which, in the investigator's assessment, may interfere with the evaluation procedures or the objectives of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Controlled Study of the Effect of Cardiovascular Exercise in Uncontrolled Epilepsy: Efficacy, Side Effects and Quality of Life
This is an open-label randomized controlled tria testing if an improvement in cardiovascular fitness can improve quality of Life and reduce seizure frequency in patients with refractory epilepsy.. Before the intervention each subject will undergo an evaluation of baseline cardiovascular fitness. Patients will be randomized into two groups One group will listen to a relaxation tape 5 days per week for 6 months and the other group will receive a ergometric cycle and perform a predetermined level of exercise per day , 5 days per week for 6 months. Randomization will be conducted an external randomization center based on a sequence of random numbers.
Changes in concomitant antiepileptic drugs (AED) treatment during the study will be minimized, and restricted to AED changes deemed to be necessary to address AED-related toxicity.
Read more
Medical examination; body weight; fitness test, including ECG and BP measurements, seizure frequency; adverse effects (unstructured interview); details of concomitant concomitant treatment, mood assessment by using the Hospital Anxiety and Depression Scale-Anxiety (HADS); health related quality of life (RAND-36), E4-data downloading, will be done at baseline and after 6 months
Primary endpoint: Proportion of patients with at least 50% seizure reduction
Secondary endpoints: Median percent reduction in seizure frequency, HADS score, RAND-36 score, fitness score; adverse events, changes in concomitant AED treatment, E4 data
.
Read the detailed description
Objectives
The primary objective of this study is to assess the effect of a 6-month course of standardized physical exercise, added on to pre-existing stable AED treatment, on seizure frequency in patients with epilepsy aged 16 to 65.
Secondary objectives include the assessment of the effect of a 6-month course of standardized physical exercise, added on to pre-existing stable AED treatment, on (i) depressive and anxiety symptom scores; (2) health-related quality of life; (3) adverse
events.
Study design
Open-label randomized controlled trial. Before the intervention each subject will undergo an evaluation of cardiovascular fitness using the cycle ergometric test and his/her work level ((Wmax/kg) transformed into a stanine (1-9) score. Patients will be randomized into two groups by applying a stratification procedure which will allow a similar proportion of patients with high fitness (stanine score 5 to 9) and low fitness (stanine score 1 to 4) in both groups. Randomization will be conducted by telephone through an external randomization center based on a sequence of random numbers.
Of the two randomized groups, one (Intervention group) will receive a course of standardized physical exercise for at least 5 days per week while the other group (control group) will randomize to listening to a computerized disc (CD) on muscular relaxation..
Changes in concomitant AED treatment during the study will not be allowed unless for adverse events related to the AEDs.
Study procedures
Patients considered to be eligible for the study will undergo initially a 4-week prospective baseline to ascertain baseline seizure frequency. After confirming their eligibility based on seizure frequency recording, patients will be examined by a study physician and by a physical therapist who will conduct an ergonomic test with a stationary bicycle under ECG and blood pressure monitoring to determine the level of cardiovascular fitness required for stratification. Thereafter the patients will be randomized to the intervention and the control group.
The intervention group will receive a course of standardized physical exercise designed to fulfill the Swedish recommendations (FYSS) on exercise for disease-prevention (150 min per week of average intensity); at least 5 days per week for 6 months using a bicycle ergometer for 30 minutes a day. An individually adjusted workload will be determined by the physical therapist to achieve moderate intensity workout based on maximal oxygen uptake (VO2)max and percentage of maximal heart rate. Patients in the other group (control group) will be randomized to listen to a CD on muscular relaxation every day for 20 minutes and continue with their usual lifestyle. At enrollment, subjects randomized to the intervention group will be provided with a bicycle ergometer. requirements) as well parameters related to seizure activity.
The following evaluations will be conducted at the times indicated, which correspond to hospital visits:
Time 0 (enrollment): Medical examination; body weight; fitness test (Åstrand submax test, which is a submaximal test of aerobic fitness.), including ECG and BP measurements, seizure frequency (last 4 weeks); adverse effects (unstructured interview); details of concomitant concomitant treatment, mood assessment by using the Hospital Anxiety and Depression Scale-Anxiety (HADS); health related quality of life (RAND-36).
Month 1, 2, 3, 4 and 5: Seizure frequency (recorded daily on seizure calendars), adverse effects (unstructured interview); body weight; details of concomitant treatment, E4-data downloading, advice on exercise from physical therapist.
Month 6: Medical examination; body weight; fitness test, including ECG and BP measurements, seizure frequency; adverse effects (unstructured interview); details of concomitant concomitant treatment, mood assessment by using the Hospital Anxiety
and Depression Scale-Anxiety (HADS); health related quality of life (RAND-36), E4-data downloading,
Any additional testing (e.g. EEG, laboratory tests) may be performed as considered clinically indicated by the treating physician.
Sample size and statistical analysis
Assuming that 40% of patients in the intervention group vs. 20% of patients in the control group have a 50% or greater reduction in seizure frequency compared with baseline, 79 patients per group provide 80% power to identify a difference between groups at a significance level of 0.05. To account for potential dropouts, a total of 100 patients per group will be randomized.
The primary analysis will be intent-to-treat (ITT) using "The Last Observation Carried Forward " (LOCF) extrapolation when appropriate. Per-protocol analysis (PPT) will exclude patients discontinuing prematurely the study and patients with less than 75% compliance with exercise requirements.
Ethical aspects
The study protocol has been approved by the Ethics Committees of Gothenburg in behalf of the participating centers. Before the study, all patients will be informed about the objectives and implications of the study, and will be asked to sign an informed consent form.
- Conditions
- Refractory Epilepsy
- Being tested
- Exercise, Relaxation
- Keywords
- Cardiovascular fitness, refractory epilepsy,
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseBehavioural
Also called cardiovascular fitness
Patients will bicycle for 20 minutes per day for 5 days per week for 6 months
RelaxationBehavioural
Patients will listen to a relaxation tape 20 minutes per day 5 Days a week for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Exercise | Active comparator | Use of an ergometric bicycle where patients will bicycle 5 Days a week for 20 minutes at a predetermine level Receives: Behavioral: Exercise |
| Relaxation | Sham comparator | Patients will listen to a relaxation exercise involving muscle relaxation. This takes about 20 minutes and will be performed 5 Days/week Receives: Behavioral: Relaxation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with at least 50% seizure reduction
Determined by seizure diary
Measured: Change from baseline at 6months
Secondary outcomes (4)
Change in anxiety and depression ratings
Reduction in Hospital Anxiety and Depression Scale (HAD) scores.The HADS is a fourteen item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3. A total score can be between 0 and 21 for either anxiety or depression. A lower score indicates less depression or anxiety: a cut-off point of 8/21 indicates the presence of anxiety or depression
Measured: Change from Baseline at 6 months
Change in Health-Related Quality of Life
Improvement in "RAND-36 -Measure of Health Related Quality of Life" version called Item Health Survey (Version 1.0) score. There are 8 domains with 36 items in total. The eight health concepts are: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain and general health perceptions. All items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In a second step, items in the same scale are averaged together to create the 8 scale scores. Scores represent the percentage of total possible score achieved.
Measured: Change from Baseline at 6 months
Reduction in adverse event reporting
Subjective reporting by patient
Measured: Improvement from baseline at 6 months
Median percent change in seizure frequency
Seizure Counts by seizure diary
Measured: Change from Baseline at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2018
- Study start30 Nov 2018
- Primary completion6 Oct 2021
- Study completion6 Oct 2021
Why it stopped: Could not recruit patients because of Covid 19 restrictions and because of lack of efficacy for primary endpoint
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open label randomized parallel design
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Elinor Ben-Menachem, MD,PhD, Principal investigator, University of Gothenburg, Department of Clincial Neuroscience, Sahlgrenska Academy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03570489
- Sponsor's protocol ID
- ALFGBG-818131
- Acronym
- Epilepsy
- Status last verified
- Oct 2019
- First submitted
- 28 May 2018
- Last updated
- 15 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The plan is to share but we are uncertain just now as to how
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Study of the Effect of Cardiovascular Exercise in Uncontrolled Epilepsy: Efficacy, Side Effects and Quality of Life
- ClinicalTrials.gov ID
- NCT03570489
- Acronym / sponsor ID
- Epilepsy / ALFGBG-818131
- Conditions
- Refractory Epilepsy
- Keywords
- Cardiovascular fitness, refractory epilepsy,
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Could not recruit patients because of Covid 19 restrictions and because of lack of efficacy for primary endpoint
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Study start
- 30 Nov 2018 (actual)
- Primary completion
- 6 Oct 2021 (actual)
- Study completion
- 6 Oct 2021 (actual)
- First posted
- 27 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label randomized controlled tria testing if an improvement in cardiovascular fitness can improve quality of Life and reduce seizure frequency in patients with refractory epilepsy.. Before the intervention each subject will undergo an evaluation of baseline cardiovascular fitness. Patients will be randomized into two groups One group will listen to a relaxation tape 5 days per week for 6 months and the other group will receive a ergometric cycle and perform a predetermined level of exercise per day , 5 days per week for 6 months. Randomization will be conducted an external randomization center based on a sequence of random numbers.
Changes in concomitant antiepileptic drugs (AED) treatment during the study will be minimized, and restricted to AED changes deemed to be necessary to address AED-related toxicity.
Medical examination; body weight; fitness test, including ECG and BP measurements, seizure frequency; adverse effects (unstructured interview); details of concomitant concomitant treatment, mood assessment by using the Hospital Anxiety and Depression Scale-Anxiety (HADS); health related quality of life (RAND-36), E4-data downloading, will be done at baseline and after 6 months
Primary endpoint: Proportion of patients with at least 50% seizure reduction
Secondary endpoints: Median percent reduction in seizure frequency, HADS score, RAND-36 score, fitness score; adverse events, changes in concomitant AED treatment, E4 data
.
Detailed description
Objectives
The primary objective of this study is to assess the effect of a 6-month course of standardized physical exercise, added on to pre-existing stable AED treatment, on seizure frequency in patients with epilepsy aged 16 to 65.
Secondary objectives include the assessment of the effect of a 6-month course of standardized physical exercise, added on to pre-existing stable AED treatment, on (i) depressive and anxiety symptom scores; (2) health-related quality of life; (3) adverse
events.
Study design
Open-label randomized controlled trial. Before the intervention each subject will undergo an evaluation of cardiovascular fitness using the cycle ergometric test and his/her work level ((Wmax/kg) transformed into a stanine (1-9) score. Patients will be randomized into two groups by applying a stratification procedure which will allow a similar proportion of patients with high fitness (stanine score 5 to 9) and low fitness (stanine score 1 to 4) in both groups. Randomization will be conducted by telephone through an external randomization center based on a sequence of random numbers.
Of the two randomized groups, one (Intervention group) will receive a course of standardized physical exercise for at least 5 days per week while the other group (control group) will randomize to listening to a computerized disc (CD) on muscular relaxation..
Changes in concomitant AED treatment during the study will not be allowed unless for adverse events related to the AEDs.
Study procedures
Patients considered to be eligible for the study will undergo initially a 4-week prospective baseline to ascertain baseline seizure frequency. After confirming their eligibility based on seizure frequency recording, patients will be examined by a study physician and by a physical therapist who will conduct an ergonomic test with a stationary bicycle under ECG and blood pressure monitoring to determine the level of cardiovascular fitness required for stratification. Thereafter the patients will be randomized to the intervention and the control group.
The intervention group will receive a course of standardized physical exercise designed to fulfill the Swedish recommendations (FYSS) on exercise for disease-prevention (150 min per week of average intensity); at least 5 days per week for 6 months using a bicycle ergometer for 30 minutes a day. An individually adjusted workload will be determined by the physical therapist to achieve moderate intensity workout based on maximal oxygen uptake (VO2)max and percentage of maximal heart rate. Patients in the other group (control group) will be randomized to listen to a CD on muscular relaxation every day for 20 minutes and continue with their usual lifestyle. At enrollment, subjects randomized to the intervention group will be provided with a bicycle ergometer. requirements) as well parameters related to seizure activity.
The following evaluations will be conducted at the times indicated, which correspond to hospital visits:
Time 0 (enrollment): Medical examination; body weight; fitness test (Åstrand submax test, which is a submaximal test of aerobic fitness.), including ECG and BP measurements, seizure frequency (last 4 weeks); adverse effects (unstructured interview); details of concomitant concomitant treatment, mood assessment by using the Hospital Anxiety and Depression Scale-Anxiety (HADS); health related quality of life (RAND-36).
Month 1, 2, 3, 4 and 5: Seizure frequency (recorded daily on seizure calendars), adverse effects (unstructured interview); body weight; details of concomitant treatment, E4-data downloading, advice on exercise from physical therapist.
Month 6: Medical examination; body weight; fitness test, including ECG and BP measurements, seizure frequency; adverse effects (unstructured interview); details of concomitant concomitant treatment, mood assessment by using the Hospital Anxiety
and Depression Scale-Anxiety (HADS); health related quality of life (RAND-36), E4-data downloading,
Any additional testing (e.g. EEG, laboratory tests) may be performed as considered clinically indicated by the treating physician.
Sample size and statistical analysis
Assuming that 40% of patients in the intervention group vs. 20% of patients in the control group have a 50% or greater reduction in seizure frequency compared with baseline, 79 patients per group provide 80% power to identify a difference between groups at a significance level of 0.05. To account for potential dropouts, a total of 100 patients per group will be randomized.
The primary analysis will be intent-to-treat (ITT) using "The Last Observation Carried Forward " (LOCF) extrapolation when appropriate. Per-protocol analysis (PPT) will exclude patients discontinuing prematurely the study and patients with less than 75% compliance with exercise requirements.
Ethical aspects
The study protocol has been approved by the Ethics Committees of Gothenburg in behalf of the participating centers. Before the study, all patients will be informed about the objectives and implications of the study, and will be asked to sign an informed consent form.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open label randomized parallel design
| Arm | Type | Receives |
|---|---|---|
| Exercise | Active comparator | Behavioral: ExerciseUse of an ergometric bicycle where patients will bicycle 5 Days a week for 20 minutes at a predetermine level |
| Relaxation | Sham comparator | Behavioral: RelaxationPatients will listen to a relaxation exercise involving muscle relaxation. This takes about 20 minutes and will be performed 5 Days/week |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Age 16 years to 65 years
- An established diagnosis of focal epilepsy
- A frequency of at least 3 focal seizures (including focal to bilateral tonic-clonic) during a 4 week-prospective baseline, despite ongoing treatment with one to 4 AEDs
- Stable AED treatment for at least 4 weeks, and no expected need to modify current AED treatment over the subsequent 6 months.
- Capability to follow instructions (or has a caretaker who will help) and keep a seizure calendar
Key exclusion criteria (7 listed)
- Any associated condition contraindicating non-competitive physical exercise
- Patients already engaged in regular daily physical exercise program;
- A history of seizures induced by exercise
- A history of psychogenic non-epileptic seizures
- Pregnancy or puerperium
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExerciseAlso: cardiovascular fitnessPatients will bicycle for 20 minutes per day for 5 days per week for 6 months | Behavioural | Exercise |
| RelaxationPatients will listen to a relaxation tape 20 minutes per day 5 Days a week for 6 months | Behavioural | Relaxation |
Primary outcome
Proportion of patients with at least 50% seizure reduction
Time frame: Change from baseline at 6months
Determined by seizure diary
4 secondary outcomes
Change in anxiety and depression ratings
Time frame: Change from Baseline at 6 months
Change in Health-Related Quality of Life
Time frame: Change from Baseline at 6 months
Reduction in adverse event reporting
Time frame: Improvement from baseline at 6 months
Median percent change in seizure frequency
Time frame: Change from Baseline at 6 months
Results and safety
The study was stopped early (reason given: Could not recruit patients because of Covid 19 restrictions and because of lack of efficacy for primary endpoint). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2021.
- Individual participant dataSharing planned: Undecided. The plan is to share but we are uncertain just now as to how
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elinor Ben-Menachem, MD,PhD principal investigator
University of Gothenburg, Department of Clincial Neuroscience, Sahlgrenska Academy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise and Relaxation in people with Refractory Epilepsy, run by Vastra Gotaland Region at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Could not recruit patients because of Covid 19 restrictions and because of lack of efficacy for primary endpoint). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with at least 50% seizure reduction (time frame: Change from baseline at 6months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2021.