Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-03-30 @ 1:16 AM
Study NCT ID:
NCT07435402
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-27
First Post:
2026-01-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Reduction of Muscle Catabolism Through Brain Activation in Burn Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016638', 'term': 'Critical Illness'}, {'id': 'D018908', 'term': 'Muscle Weakness'}], 'ancestors': [{'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009135', 'term': 'Muscular Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D020879', 'term': 'Neuromuscular Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups: a control group receiving standard burn care and conventional rehabilitation with intravenous sedation, and an intervention group receiving standard burn care plus the Burn-Bundle Extended Rehabilitation Program, including inhalational isoflurane sedation and multimodal neurorehabilitation. Participants will remain in their assigned group for the duration of the study.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-05-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2030-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-21', 'studyFirstSubmitDate': '2026-01-05', 'studyFirstSubmitQcDate': '2026-02-21', 'lastUpdatePostDateStruct': {'date': '2026-02-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DEXA)', 'timeFrame': 'From baseline (within first 7 days after ICU admission) up to 24 weeks.', 'description': 'Change in lean body mass measured by dual-energy X-ray absorptiometry. Lean mass is reported in kilograms (kg).'}, {'measure': 'Change in rectus femoris muscle thickness assessed by ultrasound', 'timeFrame': 'From baseline (day 10 after injury) to day 30 after injury', 'description': 'Change in rectus femoris muscle thickness measured by ultrasound. Muscle thickness is reported in millimeters (mm).'}, {'measure': 'Change in muscle strength assessed by the Medical Research Council (MRC) Sum Score', 'timeFrame': 'From baseline (within first 7 days after ICU admission) up to 24 weeks.', 'description': 'Muscle strength assessed using the Medical Research Council (MRC) Sum Score. The MRC Sum Score ranges from 0 to 60, with higher scores indicating greater muscle strength.'}], 'secondaryOutcomes': [{'measure': 'Intensive care unit length of stay', 'timeFrame': 'From ICU admission up to 24 weeks.', 'description': 'Length of stay in the intensive care unit measured in days.'}, {'measure': 'Ventilator-free days', 'timeFrame': 'From ICU admission up to 24 weeks.', 'description': 'Number of days alive and free from invasive mechanical ventilation during the ICU stay.'}, {'measure': 'Mitochondrial oxidative phosphorylation capacity', 'timeFrame': 'Days 10, 20, and 30 after injury', 'description': 'Oxidative phosphorylation capacity measured by high-resolution respirometry in skeletal muscle biopsy samples. Results reported as oxygen flux (pmol O2·s-¹·mg-¹).'}, {'measure': 'Myokine profiles', 'timeFrame': 'During hospitalization (days 10, 20, and 30 after injury).', 'description': 'Plasma concentrations of selected myokines measured using multiplex immunoassays. Results reported in pg/mL.'}, {'measure': 'Cognitive function assessed using the Montreal Cognitive Assessment (MoCA). The MoCA score ranges from 0 to 30, with higher scores indicating better cognitive performance.', 'timeFrame': 'At hospital discharge, 3 months, and 6 months after discharge.', 'description': 'Cognitive function assessed using the Montreal Cognitive Assessment (MoCA). The MoCA score ranges from 0 to 30, with higher scores indicating better cognitive performance.'}, {'measure': 'Health-related quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)', 'timeFrame': 'At hospital discharge, 3 months, and 6 months after discharge', 'description': 'Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The EQ-5D-5L index score typically ranges from values below 0 (worse than death) to 1 (full health). Higher scores indicate better health status.'}, {'measure': 'Fatty acid oxidation capacity of skeletal muscle mitochondria', 'timeFrame': 'Days 10, 20, and 30 after injury', 'description': 'Fatty acid oxidation capacity measured by high-resolution respirometry in skeletal muscle biopsy samples, reported as oxygen flux (pmol O2·s-¹·mg-¹).'}, {'measure': 'Mitochondrial respiratory control ratio', 'timeFrame': 'Days 10, 20, and 30 after injury', 'description': 'Respiratory control ratio calculated as the ratio of ADP-stimulated respiration to resting respiration.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['extensive burn injury', 'skeletal muscle wasting', 'brain activation'], 'conditions': ['Burns - Multiple', 'Critical Illness', 'Muscle Weakness']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', 'citation': 'No publications available at this time.'}], 'seeAlsoLinks': [{'url': 'https://www.fnkv.cz', 'label': 'General information about the study and study site'}]}, 'descriptionModule': {'briefSummary': 'Patients with extensive burn injuries frequently develop severe skeletal muscle wasting and weakness as part of critical illness-related myopathy and neuropathy. This condition delays ventilator weaning, prolongs intensive care unit (ICU) and hospital stay, and contributes to long-term functional impairment and reduced quality of life. In burn patients, muscle loss is particularly pronounced during the early post-injury phase and is associated with mitochondrial dysfunction and altered neuromuscular signaling.\n\nEffective strategies to prevent muscle catabolism in critically ill burn patients remain limited. Although early active rehabilitation is beneficial, many patients are unable to participate due to deep sedation, mechanical ventilation, or clinical instability. Therefore, innovative rehabilitation approaches applicable during the acute phase of critical illness are needed.\n\nThe REMBRANT (REduction of Muscle catabolism through BRAin activation in burn patieNTs) study is a single-center, randomized, controlled, open-label clinical trial evaluating whether a multimodal brain-activating rehabilitation strategy can attenuate skeletal muscle loss in adult patients with severe burns. Thirty patients with burns involving more than 30% of total body surface area who require invasive mechanical ventilation and prolonged sedation will be randomized in a 1:1 ratio to standard care or an intervention group.\n\nBoth groups will receive standardized burn treatment and conventional rehabilitation. The intervention group will additionally receive the Burn-Bundle Extended Rehabilitation Program, combining inhalational isoflurane sedation with functional proprioceptive stimulation, repetitive transcranial magnetic stimulation, and virtual reality-assisted rehabilitation when clinically feasible.\n\nThe primary outcome is change in skeletal muscle mass and strength. Secondary outcomes include ICU length of stay, ventilator-free days, mitochondrial function, and health-related quality of life.', 'detailedDescription': 'Critically ill patients with extensive burn injuries are at exceptionally high risk of developing profound skeletal muscle wasting and weakness as part of critical illness-related myopathy and neuropathy (CRIMYNE). This condition represents a major determinant of short- and long-term outcomes, contributing to delayed ventilator weaning, prolonged intensive care unit (ICU) and hospital length of stay, impaired rehabilitation, and persistent functional disability after discharge. In patients with large burns, muscle loss is particularly rapid and severe during the early post-injury phase, frequently exceeding 1 kg of lean body mass per day, and is accompanied by mitochondrial dysfunction, systemic inflammation, altered myokine signaling, and neurodegenerative changes affecting central, peripheral, and autonomic nervous systems.\n\nDespite extensive research, effective preventive or therapeutic strategies to limit skeletal muscle catabolism in critically ill burn patients remain limited. Nutritional optimization, pharmacological interventions, and passive or assisted rehabilitation techniques have demonstrated minimal or inconsistent benefit. Active rehabilitation remains the only proven preventive approach; however, a substantial proportion of burn patients are unable to participate due to deep sedation, invasive mechanical ventilation, hemodynamic instability, prone positioning, unstable fractures, or the extent and severity of burn injuries. Consequently, there is a critical unmet need for rehabilitation strategies that can be applied safely and effectively during the early acute phase of critical illness.\n\nRecent advances in neurorehabilitation suggest that activation of central motor pathways may exert anti-catabolic effects on skeletal muscle even in immobilized or unconscious patients. Functional proprioceptive stimulation (illusory movements induced by focal muscle vibration) activates cortical motor areas and has been shown to promote antidegenerative processes within the nervous system and skeletal muscle. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique capable of modulating cortical excitability and enhancing neuroplasticity, with established safety and efficacy in various neurological and movement disorders. Virtual reality (VR)-assisted rehabilitation provides immersive multisensory stimulation and may enhance motor network activation and engagement in conscious patients.\n\nSedation strategy is another critical determinant of neurological and functional outcomes in critically ill patients. Conventional intravenous sedatives, including propofol, dexmedetomidine, and benzodiazepines, are associated with adverse effects such as hemodynamic instability, prolonged awakening, delirium, drug accumulation, and potential neurodegenerative effects. Inhalational sedation with isoflurane represents a validated alternative that allows predictable awakening, preservation of spontaneous breathing, reduced opioid requirements, and potentially improved neurocognitive outcomes. Its use may facilitate daily sedation interruptions and early rehabilitation strategies in ICU patients.\n\nThe REMBRANT (REduction of Muscle catabolism through BRAin activation in burn patieNTs) study is a single-center, randomized, controlled, open-label clinical trial designed to evaluate whether a multimodal brain-activating rehabilitation strategy can attenuate skeletal muscle catabolism and improve functional outcomes in adult patients with extensive burn injuries. The study aims to integrate optimized sedation with innovative neurorehabilitation techniques to target the central mechanisms contributing to muscle wasting in critical illness.\n\nA total of 30 adult patients with burns involving more than 30% of total body surface area (TBSA), admitted to the ICU and expected to require invasive mechanical ventilation and continuous sedation for at least seven days, will be enrolled. Participants will be randomized in a 1:1 ratio to either a control group receiving standard care or an intervention group receiving the Burn-Bundle Extended Rehabilitation Program. The study is conducted at a single specialized burn center to ensure standardized implementation of complex interventions and uniform data acquisition.\n\nBoth groups will receive standardized burn care and conventional rehabilitation according to institutional protocols. The control group will be sedated using standard intravenous sedatives, including propofol and/or dexmedetomidine. The intervention group will undergo inhalational sedation with isoflurane for the required duration of sedation. In addition, the intervention group will receive the Burn-Bundle Extended Rehabilitation Program, consisting of functional proprioceptive stimulation, repetitive transcranial magnetic stimulation, and virtual reality-assisted rehabilitation when consciousness allows. Functional proprioceptive stimulation will be applied twice daily during the early acute phase after burn injury, while rTMS will be administered once daily to potentiate cortical activation. Virtual reality-based interventions will be introduced in conscious patients as part of semi-active rehabilitation.\n\nThe primary objective of the study is to evaluate the effect of the intervention on skeletal muscle quantity and functional status during hospitalization and after discharge. Skeletal muscle mass and body composition will be assessed using dual-energy X-ray absorptiometry (DEXA), ultrasound measurement of the rectus femoris muscle, and anthropometric assessments. Functional status will be evaluated using standardized functional tests, including the Medical Research Council (MRC) sum score.\n\nSecondary objectives include assessment of ICU length of stay, ventilator-free days, cognitive recovery, and quality of life. Quality of life will be evaluated using the EQ-5D-5L questionnaire at discharge and during follow-up visits at 3 and 6 months after hospital discharge. Cognitive recovery will be assessed using standardized clinical evaluations appropriate for critically ill patients.\n\nA key mechanistic component of the study involves detailed metabolic and molecular analyses of skeletal muscle. Muscle biopsies obtained during routine surgical procedures will be used to assess mitochondrial bioenergetics using high-resolution respirometry. Parameters of mitochondrial function, including oxidative phosphorylation capacity, fatty acid oxidation, and respiratory control ratios, will be analyzed to determine the impact of the intervention on muscle energy metabolism.\n\nIn parallel, circulating and intramuscular myokine profiles will be analyzed using multiplex immunoassays. Selected myokines involved in muscle metabolism, inflammation, and neuro-muscular signaling will be measured in plasma samples and muscle biopsies at predefined time points during hospitalization. These analyses aim to elucidate the molecular mechanisms underlying muscle catabolism and recovery and to identify potential biomarkers associated with response to rehabilitation.\n\nThe study will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines, and applicable local regulatory requirements. Written informed consent will be obtained from all participants or their legally authorized representatives prior to study inclusion. The study protocol has been approved by the local Ethics Committee.\n\nBy combining optimized inhalational sedation with innovative neurorehabilitation techniques applicable during the acute phase of critical illness, the REMBRANT study aims to establish a novel therapeutic approach to limit skeletal muscle wasting in critically ill burn patients. The results of this study may provide important insights into central mechanisms of muscle catabolism and recovery and contribute to improved short-term clinical outcomes as well as long-term functional recovery and quality of life in this vulnerable patient population.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adults aged 18 years or older\n* Severe burn injury involving more than 30% of total body surface area (TBSA)\n* Admission to the intensive care unit\n* Expected need for invasive mechanical ventilation and continuous sedation for at least 7 days\n* Ability to obtain written informed consent from the patient or a legally authorized representative\n\nExclusion Criteria:\n\n* Pre-existing severe neuromuscular or neurodegenerative disease\n* Known contraindication to inhalational sedation with isoflurane\n* Pregnancy or breastfeeding\n* Participation in another interventional clinical trial that could interfere with the study outcomes\n* Any condition that, in the opinion of the investigator, would make participation in the study unsafe or interfere with protocol adherence'}, 'identificationModule': {'nctId': 'NCT07435402', 'acronym': 'REMBRANT', 'briefTitle': 'Reduction of Muscle Catabolism Through Brain Activation in Burn Patients', 'organization': {'class': 'OTHER', 'fullName': 'Charles University, Czech Republic'}, 'officialTitle': 'Reduction of Muscle Catabolism Through Brain Activation in Burn Patients (REMBRANT)', 'orgStudyIdInfo': {'id': 'REMBRANT-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'Propofol Group', 'description': 'Standard Burn Care with Intravenous Sedation'}, {'type': 'EXPERIMENTAL', 'label': 'Isoflurane Group', 'description': 'Burn-Bundle Extended Rehabilitation Program with Isoflurane Sedation', 'interventionNames': ['Other: Burn-Bundle Extended Rehabilitation Program', 'Drug: Isoflurane Inhalational Sedation', 'Device: Functional Proprioceptive Stimulation', 'Device: Neurorehabilitation Techniques']}], 'interventions': [{'name': 'Burn-Bundle Extended Rehabilitation Program', 'type': 'OTHER', 'description': 'A multimodal brain-activating rehabilitation program consisting of inhalational isoflurane sedation combined with functional proprioceptive stimulation, repetitive transcranial magnetic stimulation, and virtual reality-assisted rehabilitation when consciousness allows, applied during the acute phase after severe burn injury.', 'armGroupLabels': ['Isoflurane Group']}, {'name': 'Isoflurane Inhalational Sedation', 'type': 'DRUG', 'description': 'Sedation with inhaled isoflurane administered via an anesthetic conserving device during invasive mechanical ventilation, used as an alternative to standard intravenous sedatives.', 'armGroupLabels': ['Isoflurane Group']}, {'name': 'Functional Proprioceptive Stimulation', 'type': 'DEVICE', 'description': 'Illusory movements induced by focal vibration of muscle attachments to activate central motor pathways, applied twice daily during the acute phase of critical illness.', 'armGroupLabels': ['Isoflurane Group']}, {'name': 'Neurorehabilitation Techniques', 'type': 'DEVICE', 'description': 'Non-invasive neurorehabilitation techniques including repetitive transcranial magnetic stimulation and virtual reality-assisted rehabilitation applied to enhance cortical activation and neuroplasticity in critically ill burn patients when clinically feasible.', 'armGroupLabels': ['Isoflurane Group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '100 34', 'city': 'Prague', 'state': 'Česká Republika', 'country': 'Czechia', 'contacts': [{'name': 'Robert Zajíček, MD, PhD', 'role': 'CONTACT', 'email': 'robert.zajicek@fnkv.cz', 'phone': '+420 26716 3392'}, {'name': 'Study coordinator', 'role': 'CONTACT', 'email': 'burnsec@fnkv.cz'}], 'facility': 'University Hospital Královské Vinohrady', 'geoPoint': {'lat': 50.08804, 'lon': 14.42076}}], 'centralContacts': [{'name': 'Bohumil Bakalář, MD, PhD', 'role': 'CONTACT', 'email': 'bohumil.bakalar@lf3.cuni.cz', 'phone': '+420 728816095'}, {'name': 'Břetislav Lipový, MD, PhD, MBA', 'role': 'CONTACT', 'email': 'bretislav.lipovy@fnkv.cz', 'phone': '+420 26716 3392'}], 'overallOfficials': [{'name': 'Bohumil Bakalář, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital Kralovske Vinohrady Praha Czech Republic'}]}, 'ipdSharingStatementModule': {'url': 'https://www.fnkv.cz', 'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR', 'ANALYTIC_CODE'], 'timeFrame': 'Beginning after publication of the primary study results.', 'ipdSharing': 'YES', 'description': 'Individual participant data (IPD) underlying the results of this study will be shared upon reasonable request after publication of the primary results. Shared data will be de-identified to protect participant privacy. Requests will be reviewed by the study investigators and access will be granted for scientifically valid research proposals, subject to appropriate data use agreements and applicable ethical and legal approvals.', 'accessCriteria': 'Access to de-identified individual participant data will be granted upon reasonable request for scientifically valid research proposals, subject to approval by the study investigators and completion of appropriate data use agreements.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Charles University, Czech Republic', 'class': 'OTHER'}, 'collaborators': [{'name': 'Masaryk University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}