Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

This is a device feasibility study, therefore participants will only be enrolled into the investigational arm and will receive the RNS System Implantation.

Following resection consistent with SoC, if there is evidence of residual tumor which cannot be resected due to invasion of hand-M1 but which is small enough to be covered by two four-electrode strips, these strips will be placed on the functional cortex of interest and secured to the dura. The location of the leads will be registered into the navigation software (either Medtronic Stealth or Brainlab). The dura will then be closed as watertight as possible, and the RNS System will be incorporated into the craniotomy on closure Prior to closure, four bone screws will be placed and registered to the intraoperative navigation system as internal fiducials to be retrieved for future procedures.

RNS System Implantation

Sarah Cornell

Max Krucoff, MD

This study uses a cranial implant to deliver cortical stimulation that, when paired with physiotherapy, will remap the brain so that critical brain functions can be protected during brain tumor surgery. This pilot study will provide initial evidence for the safety and feasibility of such a protocol which will lead to future pivotal trials that could radically change eloquent area brain surgery. For patients with otherwise incompletely resectable brain tumors, this could mean a longer life expectancy and a better quality of life.

Study Protocol: Participants will undergo a standard-of-care craniotomy for resection of low-grade glioma. If part of the lesion cannot be removed due to involvement of functional cortex, RNS (Responsive Neurostimulation System \[RNS; NeuroPace, Inc.\]) electrodes will be implanted over the tumor-invaded area(s) in five participants. Stimulation will then be optimized for each individual to disrupt the function of the invaded cortical node (e.g., hand motor area -\> hand dysfunction) (Aim 1). Over the next two months, outpatient physiotherapy will work to overcome the stim-induced deficits through gradual increases in stimulation amplitude as other, non-stimulated brain regions begin to assume its function (Aim 2). Once complete, participants will return to the OR for device explantation, repeated intraoperative mapping, and extended resection (if safe) (Aim 3).

Aim 1: Optimize stimulation to maximize stim-induced deficits and minimize side effects Rationale: To induce plasticity, stimulation parameters must be individually tuned to maximize effect and minimize side effects. Approach: After device implantation and prior to hospital discharge, stimulus settings (frequency, pulse-width, and amplitude) will be optimized to the relevant clinical response while minimizing adverse effects (e.g., focal tonus, myoclonus, or seizures) while still in the safe, inpatient setting. Outcomes: Primary Endpoints: 1) stim-induced focal clinical deficit as measured on the relevant clinical scale (e.g., manual motor score \[0-5\], picture naming \[x/10\]), repetition \[x/3\]); 2) stim-induced side effects (e.g., seizures).

Aim 2: Evaluate extent of remapping and safety of outpatient stimulation-physiotherapy protocol. Rationale: The ability to deliver chronic, outpatient stimulation is vital for practical clinical translation, yet neither its safety nor efficacy has been demonstrated. Approach: After Aim 1, a physiotherapist will assign a personalized, outpatient therapy regimen aimed at overcoming stim-induced deficits. Participants will have daily virtual sessions and return to clinic 2x/week for amplitude increases to re-induce deficits that therapy has overcome. This will continue until stimulation no longer can induce a deficit, suggesting successful functional remapping and enabling a return to the OR for further resection. Outcomes: Primary Endpoints: 1) absence of stim-related ER visits, readmissions, or serious adverse events (safety), 2) changes in intraop stimulation maps from surgery 1 to surgery 2 (induced remapping).

Aim 3: Evaluate ability to extend surgical resections and associated neurological outcomes. Rationale: Any change in functional boundaries will only be useful if it results in a safe, extended resection. Approach: Each surgery will proceed with standard-of-care intraoperative functional mapping techniques and decision making. Neurological examinations will be performed preoperatively, daily while inpatient, then again at 2-weeks and 3-months postoperatively. Extent of resection will be evaluated as 3D residual tumor volume on postoperative MRI. Outcomes: Primary Endpoint: 1) Change in residual tumor volume after second versus first resection, 2) new neurological deficits 3-months after second resection compared to before second resection. Secondary Endpoint: 1) New, temporary neurological deficits after the second surgery

A Study Using Brain Stimulation and Behavioral Therapy to Increase Extent of Resection in Low-Grade Gliomas

Inducing Functional Plasticity in Glioma-Involved Functional Cortex With Deficit-Inducing Cortical Stimulation and Targeted Behavioral Therapy to Increase Extent of Resection

Calculated as: Tumor volume after second surgery - tumor volume before second surgery. Determination of volumes will be made by an attending radiologist without knowledge of clinical outcome. Manual segmentation will be performed to measure tumor volumes based on fluid-attenuated inversion recovery (FLAIR) axial slices.

Calculated as manual muscle score (MMS) before stimulation - MMS after stimulation.

MMS is a zero-to-five scale assessed as the following:

5 - normal strength 4 - give away weakness 3 - movement against gravity 2 - movement in anti-gravity position

1 - muscle twitch 0 - no movement

3a. Calculated as picture naming score (x/10) before stimulation minus after stimulation.

3b. Calculated as sentence repitition score (x/3) before stimulation minus after stimulation.

Reported as number of unintended stimulation effects, such as myoclonus, tonus, seizures, or unpleasant sensations

Reported as number of stimulation- or physiotherapy related ER visits, readmissions, or serious adverse events

This outcome will be reported as a descriptive variable, calculated as changes in the intraoperative stimulation map obtained during surgery 2 compared to surgery 1

Any new, permanent neurological deficits resulting from the second surgery

Medical College of Wisconsin

Assistant Professor of Neurological Surgery

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Behaviors and Mental Disorders

Symptoms and General Pathology

Heart and Blood Diseases

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Infections

Diabetes Mellitus

Depressive Disorder

Syncope

Syncope, Vasovagal

Acute Coronary Syndrome

Syndrome

Fatigue

Hypotension

Depression

Heart Failure

Atrial Fibrillation

Coronary Artery Disease

Myocardial Ischemia

Coronary Disease

Myocardial Infarction

Infarction

Hypertension

Heart Diseases

Ischemia

Heart Failure, Systolic

Cerebrovascular Disorders

Systolic Murmurs

Fibromyalgia

Myofascial Pain Syndromes

Autonomic Nervous System Diseases

Primary Dysautonomias

Ischemic Attack, Transient

Tachycardia

Fatigue Syndrome, Chronic

Heart Failure, Diastolic

Tachycardia, Sinus

Panic Disorder

Arrhythmias, Cardiac

Necrosis

Vascular Diseases

Muscular Diseases

Rheumatic Diseases

Collagen Diseases

Neuromuscular Diseases

Cardiac Conduction System Disease

Unconsciousness

Consciousness Disorders

Neurobehavioral Manifestations

Neurologic Manifestations

Brain Ischemia

Encephalomyelitis

Neuroinflammatory Diseases

Chronic Disease

Disease Attributes

Orthostatic Intolerance

Anxiety Disorders

Mental Disorders

Psychotic Disorders

Tachycardia, Supraventricular

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Consecutive patients who consult a cardiologist - electrophysiologist since June 2006, regardless of the age or gender in the city of Medellin, Colombia. They could have consulted previously (considered as the enrollment date) if they had, at least, one measurement of their BP in supine position, and an immediate measurement of their BP in standing position that allows diagnosing their group of blood pressure. All patients have a record in paper and/or magnetic file and in OpenClinica.

No interventions.

Luis Eduardo Medina, MD.

Luis E Medina, MD

Jose F Florez, PhD

Jose M Cotes, PhD

The essential arterial hypotension and allostasis registry is a prospective, observational research that has the purpose of demonstrating that essential blood pressure (BP) disorders and the associated comorbidities are a result of the inappropriate allostatic response to daily life stress. This required a functioning brain orchestrating the evaluation of the threat and choosing the response, this is a mind-mediated phenomenon. If the response is excessive it contributes to high BP, if deficient to low BP, and the BP itself will identify the allostatic pattern, which in turn will play an important role in the development of the comorbidities.

To do so, consecutive patients of any age and gender that visit a cardiologist's office in Medellin, Colombia, are recruited. Individuals are classified according to their arterial BP and allostasis and follow them in time to see what kind of diseases develops the most (including BP) in the follow up according to the categorization of the characteristic chosen and after adjustment for confounder's variables. In addition, stress events with their date are registered.

HYPOTHESIS

The causes of the diseases are multifactorial.

Physical, biochemical, psychological, social, and cultural dimensions of development dynamically interact to shape the health development process.

A person´s health depends on their:

1. Biological and physiologic systems
2. External and internal environment (a) physical, b) internal behavioural and arousal state as registered by the brain.
3. Their interaction.

The allostatic mechanisms to the internal and external stressors (allostatic load) involves a network composed by:

1. Functional systems; mediated by:

   1. The Autonomic Nervous System
   2. The endocrine system
   3. The immune system
2. Structural changes: whenever the internal and/or external stressors are long lasting and/or strength enough, they may induce changes in:

   1. Epigenetic, endophenotypes, polyphenism.
   2. Plasticity
3. The interaction between a) and b).

The network response do not affect exclusively the BP, propitiating the development of comorbidities, which may prompt strategies for prevention, recognition and ultimately, treatment.

The allostatic model defines health as a state of responsiveness.

The concept of psycho-biotype: The allostasis is the result of both: biological (allostasis) and psychological (psychostasis) abilities. It is proposed that both components behave in similar direction and magnitude.

Immune disorders may be associated with the development of cancer. High BP population has a higher sympathetic and lower vagal tone, this has been associated with a decrease in the immune´s system function.

Resources and energy depletion: Terms like weathering have been used to describe how exposures to different allostatic loads gradually scrape away at the protective coating that keeps people healthy. It is postulated that High BP individuals have more resources and energy.

Essential Hypotension and Allostasis Registry

Essential Arterial Hypotension and Allostasis Registry

Clinical syncope characteristics (age of first syncope, number of syncope episodes, trauma, duration, clinical score, convulse, sphincter relaxation, etc.) Syncope cause Blood pressure group Adaptability group Prognosis

TTT protocol: describe the protocol, the time at positive response, nitroglycerine use, autonomic and hemodynamic variables.

TTT outcome for syncope: positive or negative TTT other outcomes: 1) Chronotropic incompetence, 2) arterial orthostatic hypotension, 3) carotid hypersensitivity, 4) POTS, 5) IST The relationship between TTT results and Clinical score for syncope in regard to: syncope behaviour and other orthostatic intolerance entities, symptoms and comorbidities.

The relationship between neurally mediated syncope response at the TTT and comorbidities.

EPS variables: AH, AV, CL, sino atrial conduction time (SACT), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), response to Isoproterenol, intrinsic heart rate Diagnosis: control, sick sinus syndrome, IST, chronotropic incompetence at the TTT HR at the ECG HR at the Holter monitoring HR at the TTT HRV at the Holter monitoring Syncope, cardiac or neurally mediated HR at the physical treadmill test Relationship with the blood pressure group Relationship with the adaptability group

Define how the blood pressure group and/or the adaptability group may add to the already known and include in this registry, in the diagnosis of cardiovascular complications as coronary artery disease, cerebrovascular disease, peripheral artery disease, nephropathy.

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, COPD, and others.

Mortality

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable.

Psychiatric variables:

1. Big Five Questionary (BFQ) for personality.
2. Modify of the Coping Scale (Scale of modified coping strategies)
3. Zung questionary for depression and anxiety
4. MINI in those patients with moderate or severe depression and/or anxiety at the Zung questionary

High sodium intake in the diet is recognized as a risk factor for hypertension development.

Essential hypotension population is advised to increase the sodium (at least 10 grams a day) and water intake (at least 2 liters a day), or as much as possible, several have taken Fludrocortisone (is not a exclusion criteria). Normal blood pressure population are advised to have a normal or low sodium intake. Physical exercise is recommended in both groups.

This registry is a good opportunity to test how important sodium diet is to induce hypertension, or if by the contrary adaptability could prevail over high sodium intake in this registry.

Blood pressure groups: essential hypotension and normotension and those with new essential hypertension. Adaptability groups.

The results will be adjusted for age, gender and BMI.

Consistent bradycardia in the ECG at the office and normal HR in the holter monitoring or the contrary.

There are patients with complaints that may be attributed to bradycardia, low blood pressure, hypothyroidism, or other entities.

Some patients very often have bradycardia in the ECG taken in the office and normal HR in the 24 Holter monitoring, the opposite is also possible.

Patients with bradycardia (without medication or physiological condition as exersice affecting heart rate) in at least 2 ECG (less 60 bpm) and at least 2 Holter monitoring will be analyzed,

Other variables to consider are:

Age, gender, blood pressure group, adaptability group, maximum HR in the treadmill test, white coat or masked hypertension, Tilt-Table-test result or syncope cause, Electrophysiological study if available.

The acknowledge of this phenomenon could have clinical implications in the diagnosis of sick sinus syndrome and physiopathological ones.

Bradycardia is the classical presentation form for sinus node dysfunction, mainly when associated with symptoms. Chronotropic incompetence is also a manifestation. Absence of medications with effects on the heart rate (HR) must be ruled out.

Variables

1. HR at the ECG, Holter monitoring, stress text, and at the physical examination previous to pacemaker implantation,
2. Electrophysiological study (EPS): Basic cycle length, Sino-atrial conduction time, Sinus node recovery time, Corrected sinus node recovery time, Intrinsic HR when available 3. Pacemaker variables: HR at day and night or rest time Percentage of stimulation in A and V chambers 4. Syncope: Clinical characteriscs and clinical score Tilt table test results Trans Thoracic Echocardiogram in rest and or stress text Hypothesis: patients with ANSD will start to decrease the percentage atrial stimulation.

A non invasive, beat to beat BP monitoring, with the ability to measure BP, HR, Cardiac Output and Systemic Vascular Resistance (SVR) was started to use in the EHAR registry since May 2017. A description of this variables in the three BP groups will be collected in the data base (DB).

This will allow to characterize whether SVR and/or CO maintain BP. Until now BP levels are related with prognosis. In the prognosis model SVR and CO will be add them to know what matter the most: BP levels, SVR and/or CO? In the EHAR registry a collection of the variables recognized as a risk factor for several comorbidities are available to adjust in multivariable analysis.

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others.

Cardiovascular mortality Total mortality

Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others.

Cardiovascular mortality Total mortality

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable. Comorbidities: As describe in the protocol, as a summary: 1) cardiovascular, 2) metabolic, 3) Endocrine, 4) psychiatric disorders: depression and panic disorder, 5) orthostatic intolerance: neurally mediated syncope, vasovagal syncope, inappropriate sinus tachycardia, Postural orthostatic syndrome, carotid sinus hypersensitivity; 6) others: chronic fatigue syndrome, fibromyalgia, arthritis, autoimmune diseases, pulmonary thromboembolism, OSA (obstructive sleep apnea), Alzheimer disease, Parkinson disease, others dementias, epilepsia, nephropathies, and others.

Cardiovascular mortality Total mortality

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Habits: smoke and drink

Anthropometric variables: Body mass index, waist, hip

Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, homoeostasis model assessment (HOMA), total cholesterol, LDL, HDL, triglycerides.

Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone

Electrocardiogram: HR; PR interval, QRS complex, cQT interval

Holter variables: HR, standard deviation of NN intervals (SDNN) and sympathovagal balance, at day, night and 24 hs.

ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable.

Habits: smoke and drink

Anthropometric variables: Body mass index, waist, hip

Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides.

Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone

Electrocardiogram: PR interval, QRS complex, Heart rate, cQT interval

Holter variables: HR, SDNN and sympathovagal balance, at day, night and 24 hs.

ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Blood pressure group: 1) Essential arterial hypotension, 2) normotension and 3) Essential arterial hypertension.

Adaptability group: 1) Hyper adaptable, 2) normal adaptability and 3) hypo adaptable.

Habits: smoke and drink, exercise

Anthropometric variables: Body mass index, waist, hip

Metabolic and other variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides; thyrotropine,

Holter variables: HR, standard deviation of NN intervals (SDNN) and sympathovagal balance, at day, night and 24 hs.

ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Adaptability group: Hyper adaptable, normal adaptability, hypo adaptable.

Habits: smoke and drink Anthropometric variables: Body mass index, waist, hip

Metabolic variables: Fasting glucose, 2 hs postprandial plasma glucose, insulin plasma levels, HOMA, total cholesterol, LDL, HDL, triglycerides.

Endocrine variables: plasma cortisol, free cortisol in 24 hs. urine, epinephrine, norepinephrine, metanephrines, vanilmandelic acid, ACTH, aldosterone, renin, thyrotropine, free thyroxine, triiodothyronine, testosterone

Electrocardiogram: PR interval, QRS complex, Heart rate, cQT interval

Holter variables: HR, SDNN and sympathovagal balance, at day, night and 24 hs.

ABPM: Systolic, diastolic, and heart rate, at day, night and 24 hs., BP matinal surge.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study Using Brain Stimulation and Behavioral Therapy to Increase Extent of Resection in Low-Grade Gliomas	NCT04745156	Glioma Glioma Intracra... Gliomas Benign Brain Tumor Brain Cancer Motor Cortex; L...	RNS System Impl...	18 Years - 65 Years	Medical College of Wisconsin
Essential Hypotension and Allostasis Registry	NCT02018497	Blood Pressure Depression Panic Attack Fibromyalgia POTS Inappropriate S... Coronary Heart ... Acute Coronary ... Acute Myocardia... Cerebrovascular... Transient Ische... Atrial Fibrilla... Diabetes Mellit... Cancer Systolic Heart ... Diastolic Heart... Chronic Fatigue... Syncope Vasovagal Synco...		-	CES University

Spots Global Cancer Trial Database for plasticity

Every month we try and update this database with for plasticity cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for plasticity

Every month we try and update this database with for plasticity cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for plasticity cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.