Neoplasms

All Conditions

Nervous System Diseases

Musculoskeletal Diseases

Rare Diseases

Glioma

Brain Neoplasms

Ependymoma

Craniopharyngioma

Adamantinoma

Neoplasms, Germ Cell and Embryonal

Ameloblastoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Bone Neoplasms

Bone Diseases

Germ Cells Tumors

Neuroepithelioma

Anti-Dyskinesia Agents

All Drugs and Chemicals

Cardiotonic Agents

Memantine

Antiparkinson Agents

Dopamine

Dopamine Agents

Neurotransmitter Agents

Excitatory Amino Acid Antagonists

Beginning at least two weeks prior to radiation therapy, participants receive memantine. Treatment continues for 12 weeks with periodic cognitive assessments and lab work.

Beginning at least two weeks prior to radiation therapy, participants receive a placebo. Treatment and assessment are identical to the memantine group.

Medication dosing will be overseen by one of the study neurologists, with step-wise dose reductions (5 mg intervals) allowable in the case of side effects.

A placebo that appears exactly like the study drug, memantine, will be given in a manner identical to the study drug.

Placebo

Cognitive and neurologic examinations will be conducted to assess cognitive, social, quality of life, and neurological outcomes associated with memantine will be completed at baseline prior to medication start, and at 6 weeks (end of radiation therapy), 12 weeks (discontinuation of study medication or placebo), and one year post radiation therapy.

Cognitive Assessment

Heather M. Conklin, PhD

Children with brain tumors who have had radiation therapy are at risk for problems with attention, memory, and problem solving. Such problems may cause difficulty in school and daily life. Memantine, the drug being used for this study, is not yet approved for use in children by the U.S. Food and Drug Administration. However, studies have shown some improvements in memory for patients with dementia, Attention Deficit Hyperactivity Disorder, and autism. Scientists have also used this medication for adult cancer patients receiving radiation therapy with results showing less cognitive declines over time compared to patients taking a placebo (inactive pill). These studies have also shown few side effects.

This is a pilot/feasibility study and the first known study involving children with a cancer diagnosis or brain tumor.

PRIMARY OBJECTIVES:

* To estimate the participation rate in a study of memantine used as a neuro-protective agent in children undergoing radiotherapy for localized brain tumors (low grade glioma, craniopharyngioma, ependymoma, or germ cell tumor)
* To estimate the rate of memantine medication adherence
* To estimate the rate of completion of cognitive assessments

SECONDARY OBJECTIVES:

* To estimate the effect size of change in neurobehavioral outcomes (cognitive, social, quality of life, neurologic) associated with memantine
* To evaluate the frequency and nature of memantine side effects as measured by the Systematic Assessment for Treatment Emergent Events (SAFTEE)

Participants will be randomized to take part in one of two groups:

* The Memantine Group will be prescribed memantine at a dosage following FDA-approved adult labeling. A low dose will initially be given beginning at least two weeks (± 7 days) prior to beginning radiation therapy. The dose will increase until participants reach the target dose of 20 mg/day. Memantine will be given for a total of 12 weeks.
* The Placebo Group will be prescribed identical capsules with no active drug. The placebo drug will be given in the same dose and frequency as described for the Memantine group.

Participants will undergo the same evaluations and monitoring throughout the medication phase. Assessments will be done at baseline prior to study start, with follow-up assessments at 6 weeks (end of radiation therapy), and 12 weeks (end of study medication). Psychological testing to measure attention, working memory, problem solving, intelligence and academics will be done for each participant. Caregivers will also complete questionnaires about attention, problem solving, mood and interpersonal interactions. Caregivers will also be asked to complete a questionnaire about the family's general characteristics and medical history.

At the time points noted above, blood work, vital signs and echocardiograms will be obtained, and the study neurologist will examine the participant to monitor side effects and neurological functioning. A study nurse will contact the participant once per week during the 12 weeks of medication administration to identify possible medication-related side effects and to check on rate of compliance with taking the medication. A remote app will be installed on the participant's home computer or cell phone to help remind them to take the medication and track success. At one year post medication, psychological and neurological examinations will be repeated.

Randomized, double-blind, placebo-controlled trial design.

Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors

Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors: A Pilot Study

The rates of study participation and related 90% Blyth-Still-Casella intervals, as well as their regular 90% confidence interval, will be estimated. Test of one proportion will be performed against an estimated rate of 60%. The rate will be evaluated for the group as a whole as well as separately for the memantine intervention and placebo-control groups.

The rates of medication adherence and related 90% Blyth-Still-Casella intervals, as well as their regular 90% confidence interval, will be estimated. Test of one proportion will be performed against an estimated rate of 80%. The rate will be evaluated for the group as a whole as well as separately for the memantine intervention and placebo-control groups.

The rates of completion of cognitive assessments and related 90% Blyth-Still-Casella intervals, as well as their regular 90% confidence interval, will be estimated. Test of one proportion will be performed against an estimated rate of 75%. The rate will be evaluated for the group as a whole as well as separately for the memantine intervention and placebo-control groups.

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at 6 weeks (end of radiation therapy) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 6 weeks.

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at 12 weeks (end of medication trial) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 12 weeks.

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at follow-up (up to 1 year) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 1 year.

The frequency and nature of memantine side effects as measured by the SAFTEE will be evaluated qualitatively by calculating the frequency of side effect reporting by severity rating at different time points in the medication trial and comparing these frequencies across the memantine intervention and placebo-control groups. The frequency of side effects will be compared between the intervention and placebo-control groups using at t-test or other appropriate test, depending on the data distribution features of the compared outcome.

National Cancer Institute (NCI)

St. Jude Children's Research Hospital

Symptoms and General Pathology

Ear, Nose, and Throat Diseases

Facies

Neurilemmoma

Neuroma

Neuroma, Acoustic

Neuroendocrine Tumors

Nerve Sheath Neoplasms

Peripheral Nervous System Neoplasms

Vestibulocochlear Nerve Diseases

Retrocochlear Diseases

Ear Diseases

Otorhinolaryngologic Diseases

Otorhinolaryngologic Neoplasms

Cranial Nerve Diseases

Schwannoma

Acoustic Neuroma

Neuroendocrine Tumor

Other Dietary Supplements

Omega 3 Fatty Acid

Subjects will receive omega-3 supplementation (Nature's Bounty Fish Oil 1400 mg, containing 980 mg Omega-3 per capsule), to begin taking 3 days prior to surgical resection of their vestibular schwannoma. Subjects will continue to take the omega-3 supplementation for 6 weeks post-operatively.

Subjects will receive a placebo to begin taking 3 days prior to clinical care of surgical resection of vestibular schwannoma. Subjects will continue to take the placebo for 6 weeks post-operatively.

One capsule orally twice daily beginning 3 days prior to clinical care surgical intervention and continuing 6 weeks post-operative

Omega-3

One cellulose capsule orally twice daily beginning 3 days prior to clinical care surgical intervention and continuing 6 weeks post-operative

Michael Link, MD

Lucas P Carlstrom, MD, PhD

Matthew L Carlson, MD

The purpose of this research is to develop a therapeutic agent to help improve facial nerve outcomes and ultimately improve long-term quality-of-life following surgical resection of vestibular schwannomas. It is possible the therapeutic agent may impact tumor control rates as well, and this will also be studied. Using rigorous scientific methods, we will assess whether these factors are impacted by the treatment agent (Omega-3) versus placebo control (cellulose).

Vestibular schwannomas (VS) are common, often-benign intracranial neoplasms, however surgical resection carries high risk of causing neurologic impairments that may severely impact patient quality-of-life. The most morbid common postoperative deficit is facial weakness due to the close anatomic proximity of VS with the facial nerve, which is frequently stretched and attenuated by the tumor itself, and subject to additional mechanical stress during surgery. In addition to disfiguring cosmesis, facial weakness carries the secondary effects of abnormal speech, ocular morbidity from inadequate eye closure and corneal lubrication, and dysfunctional swallowing mechanics. Some patients may eventually recover partial facial nerve function; however, this is an unreliable process that proceeds slowly over months to years, if at all. At present, no pharmacologic avenue exists for promoting facial nerve neuroprotection or regeneration. Correspondingly, the development of a therapeutic agent to stimulate improved facial nerve outcomes would markedly enhance patient outcomes and quality-of-life.

In the anterior skull base, loss of olfaction is a common sequela of following endoscopic surgical resection due to direct nerve manipulation, impacting approximately 25% of patients who undergo endoscopic endonasal tumor resection. In a recent randomized clinical trial, postoperative supplementation with omega-3 yielded a significant, sustained 1-2-point improvements on the University of Pennsylvania Smell Identification Test as assessed at six weeks, three months, and six months post-operatively. Although mechanistic understanding of the relationship between omega-3 supplementation and olfactory function preservation is incompletely understood, preliminary data support the hypothesis of direct neural regeneration and/or neuro-protective effects through anti-demyelination effects. More specifically, polyunsaturated fatty acids have been shown to modulate neural plasticity and provide a protective role in maintaining functional neuronal cell membranes thought to be critical for maintaining nerve connectivity and function. It is also possible that omega-3, a known anti-inflammatory agent through reducing local IL-6, TNF, NFkB, impacts the innate immune system to mitigate demyelination and other destructive post-treatment inflammatory injuries to cranial nerves and surrounding support cells. Given the highly interrelated mechanisms-of-injury resulting in olfactory deficit after anterior skull base surgery and facial weakness after VS resection, application of omega-3 fatty acids may provide similar benefits with respect to facial nerve protection and/or rehabilitation. As a fascinating aside, new pre-clinic animal model evidence also suggests that omega-3 fatty acid supplementation may result in delayed progression in a neuroblastoma xenograft model. These effects are attributed to anti-inflammatory and anti-angiogenic effects via anti-VEGF and other anti-proliferative growth factors; factors also implicated in VS pathophysiology, suggesting that omega-3 may also impact early tumor control as well. We hypothesize that post-operative omega-3 supplementation will improve facial nerve function following resection of vestibular schwannomas and enhance early tumor control rates.

Randomized, double-blinded, placebo-controlled clinical trial

All patients and clinical providers, including outcomes assessors, will be blinded to treatment vs placebo arms. Masking will be performed by an independent trial coordinator not involved with data collection, data analysis, or patient care.

Enhancing Facial Nerve Function With Omega-3 After Resection of Vestibular Schwannoma

Enhancing Facial Nerve Neuroprotection and Regeneration Through Omega-3 Supplementation Following Vestibular Schwannoma Resection

May be available on specific requests for collaboration.

Subjects will receive independent examination by at least three expert clinical assessors using the standardized, and clinically validated, House-Brackmann facial function score to characterize the severity of facial paralysis. Score is determined by measurements (in cm) of subjects movements of facial reference points on a scale of 0-8 which translate to grading system of grade I (normal) - Grade VI (no facial motion)

Number of subjects to have tumor recurrence or progression of vestibular schwannoma as assessed by post-operative radiography (MRI) imaging

Mayo Clinic

Principal Investigator

Behaviors and Mental Disorders

Cognitive Dysfunction

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Brain Tumor, Childhood

Central Nervous System Depressants

Psychotropic Drugs

Lithium Carbonate

Antidepressive Agents

Enzyme Inhibitors

Lithionit 42 mg (lithium sulphate, 6 mmol), start dose 1x1, then slow dose escalation using therapeutic drug monitoring (TDI) to establish a target serum level of 0.5-1.0 mmol/liter.

Identical looking placebo (white round tablet, 10 mm diameter) will be dose escalated and monitored the same way as lithium, with sham values guiding the dosing.

Lithium

White round tablet, 10 mm. Identical to experimental drug (lithium)

Klas Blomgren, MD, Professor

Gustaf Hellspong, MD, PhD Student

Gustaf Hellspong, MD

Klas Blomgren, MD, professor

Randomized, placebo-controlled, double-blinded, parallel group clinical trial to investigate if 6 months of oral lithium tablets (S-lithium 0,5-1,0 mmol/l) will prevent cognitive decline after brain radiotherapy in pediatric brain tumor survivors.

Primary outcome measure is Processing Speed Index (PSI) 2 years after start of study treatment.

Late-appearing cognitive side effects after brain radiotherapy is a potential disabling condition in pediatric brain tumor survivors. It can have profound negative effects on education, career options and quality of life. There is no current interventional drug treatment to prevent this intellectual impairment after brain tumor treatment.

Primary objective:

To assess the efficacy of lithium treatment (up to 7 years) after brain radiotherapy (both whole brain and focal) for central nervous system malignancy in preventing late-appearing cognitive processing speed impairment in children aged 5 or older.

Secondary objectives:

* To assess the efficacy of lithium treatment through evaluation of other neuropsychological/quality of life test scores.
* To assess the efficacy of lithium treatment through evaluation of radiological findings after lithium treatment using Magnetic Resonance Imaging (MRI) of the brain.

Exploratory objectives:

To explore the feasibility, safety and tolerability of lithium treatment in this patient group, using side effect forms/adverse events (AE) reporting and laboratory measures.

Randomization is based on whether or not the study participant had received radiotherapy to the whole brain (CSI) or only part of it (focal irradiation). Within each of these two arms there is a predetermined block randomization with a 2:1 lithium:placebo ratio.

Identical-looking placebo is used. S-lithium levels are masked by using a separate lab service and sham values for placebo group.

Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

* Number of potentially eligible patients identified
* Number of patients screened
* Number of patients randomized
* Number of patients completing the study per protocol
* Number of patients terminating study during IMP treatment period (6 months).
* Number of patients terminating study during follow-up period (up 5 years post IMP treatment)

* Description of reason why eligle patient declined screening
* Description of reason why screened patient was not randomized/included
* Description of reason(s) for early study termination.

Duration of IMP treatment, measured in total number of days where IMP was taken

* Numbers of IMP dose reductions
* Number of IMP temporary stops

* Descriptions of reason(s) for IMP dose reductions
* Descriptions of reason(s) for IMP temporary stops
* Descriptions of reason(s) for IMP premature (before per protocol) permanent stop.

* Number of target serum concentration measurements within target range (0.5-1.0 mmol/liter) divided by total number of measurements.
* Number of target serum concentration measurements above target range (0.5-1.0 mmol/liter) divided by total number of measurments
* Number of target serum concentration measurements below target range (0.5-1.0 mmol/liter) divided by total number of measurments

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

Cognitive processing speed. Normed score min 45, max 155. Higher = better.

* Verbal Comprehension Index (VCI)
* Visual Spatial Index (VSI)
* Fluid Reasoning Index (FRI)
* Working Memory Index (WMI)

Normed score min 45, max 155. Higher = better.

Motor speed / manual dexterity. Unit: time in seconds to complete all pegs. Lower=better.

Visual motor integration. Normed score min 1, max 19. Higher = better.

Sustained attention. Multiple T-scores, min 0, max 80. Higher = better.

Executive function and inhibition, age 8 years and above. Normed score min 1, max 19. Higher = better.

Executive function and inhibition. Normed score min 1, max 19. Higher = better.

Executive function and inhibition, age below 8 years. Normed score min 1, max 19. Higher = better.

Health related quality of life. Score min 0, max 100. Higher=better.

Loneliness scale. Score min 3, max 9. Lower = better.

Psychosocial strengths and difficulties. Score min 0, max 40.

Executive function. Score min 20, max 80.

Rigshospitalet, Denmark

Region Stockholm

Quality of Life

Antioxidants

Five times per day for 6 weeks subjects will dissolve a hydrogen generating tablet into water and drink the effervescent water. Dissolving one tablet in 250 mL of water will achieve a saturating hydrogen concentration of approximately 1.6 ppm.

Five times per day for 6 weeks subjects will dissolve an placebo tablet into water and drink the effervescent water. The effervescent placebo tablet does not generate hydrogen-enriched water.

Each hydrogen tablet contains 80 mg magnesium

Hydrogen

Matching placebo tablet also contains 80 mg magnesium

Placebo oral tablet

Agnieszka Kowalska, MD

This is a pilot randomized control trial (RCT) to explore the effects of hydrogen rich water on quality of life in patients with high grade gliomas, receiving focal radiation therapy to the brain concurrent with chemotherapy with Temozolomide.

This will be a pilot trial exploring the ability of molecular hydrogen to improve quality of life in patients with high grade gliomas, receiving focal radiation therapy to the brain concurrent with chemotherapy with Temozolomide. Hydrogen has an excellent safety profile, has antioxidant properties and reduces inflammatory events in the tissues. It has been postulated in previous studies that continuous consumption of hydrogen water reduces oxidative stress in the brain by lowering the concentration of the reactive oxygen species, resulting in the improvement of adult neurogenesis or the stimulation of neural proliferation, leading to the prevention of the decline in the learning and memory.

This will be a double blinded, placebo-controlled trial. Eligible and willing subjects will be randomly assigned in a 2:1 ratio to be treated with either hydrogen or placebo, to receive hydrogen or placebo, additionally to all standard-of-care treatments. The treatment with hydrogen or placebo will start the day before chemoradiation therapy starts, and continue for six weeks. The effects of drinking hydrogen water on the quality of life will be assessed using the EORTC QLQ-C30 and the EORTC QLQ-BN20 questionnaires at baseline, at 6 weeks, 6 months, 12 months, 18 months and 24 months.

The subjects will be randomly assigned in a 2:1 ratio to receive hydrogen or placebo, additionally to all standard-of-care treatments by the SB Research Pharmacy. Masking of active and placebo treatments will be preserved by creating study medication containers that appear identical.

Effect H2 Water on QoL of Patients Receiving Radiotherapy for High Grade Gliomas.

Pilot Study on Effects of Hydrogen Rich Water on Quality of Life of Patients Treated With Radiotherapy for High Grade Gliomas.

Feasibility of recruitment, assessment procedures, treatment, and outcome measures will be evaluated. Number of screened / eligible / enrolled patients, treatment adherence, assessment completion, subject dropout, data completeness, and data variability.

Change in health related quality of life from baseline to week 6, month 6, month 12, month 18, and month 24, as assessed by the EORTC QLQ-C30 score. The score range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

Change in health related quality of life from baseline to week 6, month 6, month 12, month 18, and month 24, as assessed by the EORTC QLQ-BN20 score. The score range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

Change in memory from baseline to week 6, month 6, month 12, month 18, and month 24, as assessed by the Mini-Mental State Examination (MMSE).

Change in Karnofsky performance score (KPS) from baseline to week 6, month 6, month 12, month 18, and month 24.

Overall survival is defined as the time from randomization until death from any cause. PFS is defined as the time from randomization until tumor progression (defined by McDonald's criteria).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors	NCT03194906	Glioma of Brain Craniopharyngio... Ependymoma Germ Cell Tumor	Memantine Placebo Cognitive Asses...	6 Years - 21 Years	St. Jude Children's Research Hospital
Enhancing Facial Nerve Function With Omega-3 After Resection of Vestibular Schwannoma	NCT05116878	Vestibular Schw...	Omega-3 Placebo	18 Years -	Mayo Clinic
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy	NCT06051240	Cognitive Impai... Cognitive Decli... Radiotherapy Si... Radiotherapy; C... Brain Tumor Memory Impairme... Late Effect of ...	Lithium Placebo	5 Years -	Region Stockholm
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy	NCT06051240	Cognitive Impai... Cognitive Decli... Radiotherapy Si... Radiotherapy; C... Brain Tumor Memory Impairme... Late Effect of ...	Lithium Placebo	5 Years -	Region Stockholm
Effect H2 Water on QoL of Patients Receiving Radiotherapy for High Grade Gliomas.	NCT04175301	Malignant Gliom...	Hydrogen Placebo oral ta...	18 Years -	Stony Brook University
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy	NCT06051240	Cognitive Impai... Cognitive Decli... Radiotherapy Si... Radiotherapy; C... Brain Tumor Memory Impairme... Late Effect of ...	Lithium Placebo	5 Years -	Region Stockholm
Effect H2 Water on QoL of Patients Receiving Radiotherapy for High Grade Gliomas.	NCT04175301	Malignant Gliom...	Hydrogen Placebo oral ta...	18 Years -	Stony Brook University
Effect H2 Water on QoL of Patients Receiving Radiotherapy for High Grade Gliomas.	NCT04175301	Malignant Gliom...	Hydrogen Placebo oral ta...	18 Years -	Stony Brook University
Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors	NCT03194906	Glioma of Brain Craniopharyngio... Ependymoma Germ Cell Tumor	Memantine Placebo Cognitive Asses...	6 Years - 21 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for neuroprotection