Trial record 1 of 1 for:
NCT03735901
Enhancement of Stroke Rehabilitation With Levodopa (ESTREL)
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| ClinicalTrials.gov Identifier: NCT03735901 |
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Recruitment Status :
Recruiting
First Posted : November 8, 2018
Last Update Posted : April 12, 2022
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Sponsor:
University Hospital, Basel, Switzerland
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
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Brief Summary:
Trial investigates the benefits and harms of Levodopa /Carbidopa 100/25mg compared to placebo (given in addition to standardized rehabilitation based on the principles of motor learning) and whether there is an association with a patient-relevant enhancement of functional recovery in acute stroke patients. Study participants will be randomized 1:1.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Stroke Stroke Rehabilitation | Drug: IMP Levodopa 100mg/Carbidopa 25mg Drug: Matching placebo | Phase 3 |
Trial investigates whether Levodopa/Carbidopa compared to placebo given in addition to standardized rehabilitative therapy in patients with acute stroke is associated with
a) patient relevant improvements of physical function b) improvement in patient-self assessed general health aspects, pain, mood, anxiety, fatigue and social participation c) long-term sustainability of a patient-relevant improvement of motor function d) improvement of selective hand and wrist movement e) a higher rate of patients walking independently of the help of another person.
f) less severe impairment g) a higher level of activity of daily living h) improvements of quality of life (i) better cognitive performance (j) no signals of harms (i.e. indications for increased all-cause mortality, recurrent stroke or serious adverse events).
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 610 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Study participants will be randomized 1:1 |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | double-blind |
| Primary Purpose: | Treatment |
| Official Title: | Enhancement of Stroke Rehabilitation With Levodopa (ESTREL): a Randomized Placebo-controlled Trial |
| Actual Study Start Date : | June 14, 2019 |
| Estimated Primary Completion Date : | December 31, 2022 |
| Estimated Study Completion Date : | December 31, 2022 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Experimental Intervention
White Investigational Medicinal Product (IMP)- capsules of a combination of IMP Levodopa 100mg/Carbidopa 25mg.
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Drug: IMP Levodopa 100mg/Carbidopa 25mg
Study treatment will comprise 3 phases:
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Placebo Comparator: Control Intervention
Matching placebo, identical in aspect, texture, and taste when compared to the IMP. Procedures regarding route of administration, study treatment duration and treatment phases will be identical in the IMP- and the placebo-group.
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Drug: Matching placebo
Study treatment will comprise 3 phases:
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Primary Outcome Measures :
- Between-group difference of scores in the Fugl-Meyer-Motor Assessment (FMMA) [ Time Frame: Assessed 3 months +/- 14 days after randomization ]FMMA is a stroke-specific impairment index designed to assess motor recovery. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale (0=cannot perform; 1=performs partially and 2= performs fully). FMMA total scores range from 0 (no movements) to 100 (normal movements) with 66 points for movements of the upper limbs (FMMA-UE) and 34 for those of the lower limbs (FMMA-LE). A difference of 5.25 points for the upper extremity and 6 points for the lower extremity part of the score are described as minimal clinically important difference. For this study, based on these data, 6 points difference are considered a patient-relevant difference between both treatment groups for the primary endpoint.
Secondary Outcome Measures :
- Change in NIH-Stroke Scale score (NIHSS) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]To objectively quantify the impairment caused by a stroke. NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
- Change in modified Rankin Scale Score (mRS) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]
Scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death.
0 - No symptoms.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead.
- Change in Stroke rehabilitation outcomes for disease specific morbidity and quality of life - PROMIS 29 [ Time Frame: Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Patient-self-assessment in the following categories: 1) physical function, 2) anxiety, 3) depression, 4) fatigue, 5) sleep disturbance, 6) ability to participate in social roles and activities, 7) pain interference and 8) pain intensity. Each of the domains 1 to 7 are assessed with 4 questions. Items are scored on 1 of 5 levels based on the ability of the participant to perform activities or the self-assessment of the participant in the various domains. Pain intensity is scored on a visual analogue scale of 0 to 10.
- Change in Stroke rehabilitation outcomes for disease specific morbidity and quality of life - PROMIS 10 [ Time Frame: Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Patient-self-assessment Patient-Reported Outcomes Measurement Information System (PROMIS) 10 addresses general health aspects, quality of life, pain, mood, anxiety, fatigue and social participation; PROMIS-10 covers the outcome domains considered most important
- Change in Patient-reported assessment of relevance of motor improvement [ Time Frame: Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Patients Questionnaire asking whether there is improvement in motor function since the last study visit and if so, whether this improvement is relevant in patients personal perception (yes/ no)
- Change in Rivermead Mobility Index (RMI) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]15 items that measure the ability of patients to make postural adjustments (e.g, move in bed), transfer (e.g. between bed to chair), walk, and use stairs and is scored from 0-15 Points. A RMI score of ≥ 7 translates into the ability of the patient walking independently of the assistance of another Person.
- mortality (of any cause) [ Time Frame: Throughout the whole study period from Day 1 to Visit 12 months +/- 30 days after randomization ]death rate
- recurrent stroke (any type) [ Time Frame: Throughout the whole study period from Day 1 to Visit 12 months +/- 30 days after randomization ]recurrent stroke (any type)
- Rate of pre- specified Adverse Events of Interest [ Time Frame: Throughout the study period from Day 1 to Visit 3 ( 3 months +/- 14 days after randomization) ]Nausea, Vomiting, Taste disturbances, Dry mouth, Anorexia, Arrhythmias, Postural hypotension Syncope (unconsciousness for a short time as a result of reduced blood flow to the brain), drowsiness (including sudden onset of sleep) Fatigue, Dementia, Psychoses (a distorted perception of reality), Hallucinations, Confusion, Euphoria, Abnormal dreams, Insomnia, Depression, Anxiety, Dizziness, Dystonia (involuntary contractions), Dyskinesia (inability to control voluntary movements), Chorea (sudden twitching of the face and shoulders)
- number of re-hospitalizations [ Time Frame: Throughout the whole study period (Visit 1 = Baseline (day 0) to Visit 12 months +/- 30 days after randomization ]re-hospitalization
- Change in Motricity Index (MI) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Two subscales, one for the upper extremity (UE) (total score range 0 to 100) and one for the lower extremity (LE) (total score range 0 to 100). It measures isometric muscle strength (0 = no movement; 100 = normal)
- Change in Trunk Control Test (TCT) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Assesses the trunk abilities of the patient , contains 4 items, with item scores ranging from 0 to 25. The sitting balance item assesses the patients' ability to sit during 30 seconds without trunk and feet support and has a predictive value for recovery of walking poststroke
- Change in Action Research Arm Test (ARAT) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Assesses the patients' ability to grasp (subscale with 6 items), grip (subscale with 4 items), pinch (subscale with 6 items) and perform gross movements (subscale with 3 items) with the upper extremity. Score: 0 = no movement / 1= movement task is partially performed / 2 = movement task is completed but takes abnormally long / 3 = movement is performed normally
- Change in Box- and Block Test (BBT) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Patients (seated in front of a square box with two compartments) are asked to move as many wooden cubes as possible from one compartment to the other within 60 seconds of testing time.
- Change in Functional Ambulation Categories (FAC) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]
Classification (score range 0 to 5) regarding the ability to walk independently, with or without a walking aid and takes the type of walking surface into account.
Rating:
0 = Patient cannot walk, or needs help from 2 or more persons
- = Patient needs firm continuous support from 1 person who helps carrying weight and with balance
- = Patient needs continuous or intermittent support of one person to help with balance and coordination
- = Patient requires verbal supervision or stand-by help from one person without physical contact
- = Patient can walk independently on level ground, but requires help on stairs, slopes or uneven surfaces
- = Patient can walk independently anywhere
- Change in Ten-Meter Walk Test (10MWT) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Walking speed and cadence over a 10 meter track at both a comfortable and a maximum Speed; time in seconds over 10-meter walking distance
- Change in Jamar dynamometer testing (JDT) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]grip strength and strength of the forearm (in kilogram)
- Change in Montreal Cognitive Assessment (MoCA) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Assesses cognitive domains: Short-term memory recall task (5 points).Visuospatial abilities assessed using clock-drawing task (3 points) and 3-dimensional cube copy (1 point). Executive functions assessed using alternation task. Attention, concentration, working memory evaluated using a sustained attention task (target detection using tapping; 1 point), serial subtraction task (3 points), digits forward and backward (1 point each). Languages assessed using 3-item confrontation naming task with low-familiarity animals (lion, camel, rhinoceros; 3 points), repetition of 2 complex sentences (2 points), and fluency task. Orientation to time and place evaluated by asking for date and city in which the test is occurring (6 points). A score of 26 or over is considered to be normal (range 0 to 30)
- Change in Daily activity measurement with movement sensor [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]Movement sensors allow assessment of physical activity engagement and upper limb use in daily life situations without physically hampering the patient in the performance of their daily activities
- Rate of Serious Adverse Event (SAE) [ Time Frame: Throughout the study period from Day 1 to Visit 3 ( 3 months +/- 14 days after randomization) ]
Any untoward medical occurrence that:
- results in death,
- is life-threatening,
- requires in-patient hospitalization or prolongation of existing hospitalisation,
- results in persistent or significant disability/incapacity, or
- is a congenital anomaly/birth defect
- Between-group difference of scores in the Fugl-Meyer-Motor Assessment (FMMA) [ Time Frame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization ]FMMA is a stroke-specific impairment index designed to assess motor recovery. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale (0=cannot perform; 1=performs partially and 2= performs fully). FMMA total scores range from 0 (no movements) to 100 (normal movements) with 66 points for movements of the upper limbs (FMMA-UE) and 34 for those of the lower limbs (FMMA-LE). A difference of 5.25 points for the upper extremity and 6 points for the lower extremity part of the score are described as minimal clinically important difference. For this study, based on these data, 6 points difference are considered a patient-relevant difference between both treatment groups for the primary endpoint.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Acute ischemic or hemorrhagic (i.e. intracerebral hemorrhage excluding subarachnoid hemorrhage and cerebal venous sinus thrombosis) stroke ≤ 7 days prior to randomization
- Clinically meaningful hemiparesis (i.e. scoring a total of ≥ 3 points on the following NIH stroke scale score items (i) motor arm, (ii) motor leg, (iii) limb ataxia; a distal arm paresis is equivalent to one of the aforementioned (i-iii))
- Time of randomization ≥24-hours since thrombolysis or thrombectomy
- In-hospital rehabilitation required
- Capable to participate in standardized rehabilitation therapy
- Informed consent of patient or next of kin
Exclusion Criteria:
- Diagnosis of Parkinson's Disease
- Use of Levodopa mandatory according to judgement of treating physician
- Inability or unwillingness to comply with study procedures including adherence to study drug intake (orally, or via nasogastric tube or percutaneous endoscopic gastrostomy tube)
- Severe aphasia (i.e. unable to follow two-stage-commands)
- Previously dependent in the basal activities of daily living (defined as modified Ranking Scale prior to stroke > 3)
- Pre-existing hemiparesis
- Known hypersensitivity to Levodopa/Carbidopa and other contraindications for Levodopa/Carbidopa as outlined in the summary of product characteristics
- Women who are pregnant or breast feeding, or who intend to become pregnant during the course of the study. Women of childbearing age must take a pregnancy test to be eligible for the study.
- Lack of safe contraception, defined as: Female Participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the Investigator in individual cases. Female Participants who are surgically sterilized / hysterectomized or post- menopausal for longer than 2 years are not considered as being of child- bearing potential.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03735901
Contacts
| Contact: Stefan Engelter, Prof. MD | +41 61 326 4063 | stefan.engelter@felixplatter.ch | |
| Contact: Christopher Tränka, Dr. med | +41 61 328 64 02 | christopher.traenka@usb.ch |
Locations
Show 24 study locations
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Swiss National Science Foundation
Investigators
| Principal Investigator: | Stefan Engelter, Prof. MD | Felix-Platter Spital Basel |
| Responsible Party: | University Hospital, Basel, Switzerland |
| ClinicalTrials.gov Identifier: | NCT03735901 |
| Other Study ID Numbers: |
2018-02021; me16Engelter |
| First Posted: | November 8, 2018 Key Record Dates |
| Last Update Posted: | April 12, 2022 |
| Last Verified: | April 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by University Hospital, Basel, Switzerland:
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Levodopa/ Carbidopa Fugl-Meyer-Motor-Assessment (FMMA) acute ischemic stroke |
acute hemorrhagic stroke Rehabilitation Recovery |
Additional relevant MeSH terms:
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Stroke Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Levodopa Carbidopa |
Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Aromatic Amino Acid Decarboxylase Inhibitors Enzyme Inhibitors |