Clinical trial NCT06051240: Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy
Official title: Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cognitive Impairment
Cognitive Decline
Radiotherapy Side Effect
Radiotherapy; Complications
Brain Tumor
Memory Impairment
Late Effect of Radiation
Keywords: lithium
neuroprotection
neuroprotective
regenerative
prevention
radiation
pediatric brain tumor
brain tumor
cognition
cognitive
Lead sponsor: Region Stockholm
Sponsor class: OTHER_GOV
Collaborators: name: Rigshospitalet, Denmark
First posted: 2023-09-22
Enrollment: 84
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age \>5 years.
* Age \<18 years at time of radiotherapy.
* Has received cranial/craniospinal radiation treatment of brain tumor within the last 7 years.
* Adequate contraceptive method to prevent pregnancy\* during the entire lithium treatment period and six months thereafter.
* Negative pregnancy test\* at screening, at start of study treatment, and monthly thereafter.
* Written informed consent from patient and/or caregiver.

Exclusion Criteria:

* Allergy/hypersensitivity to lithium or any of the excipients
* Renal failure (Cystatin C derived Glomerular Filtration Rate \< 60).
* Cardiac failure or heart disease, including Brugada syndrome (or family history thereof).
* Uncontrolled hypothyroidism.
* Pregnancy or breast feeding.
* Severe fluid or electrolyte imbalance.
* Karnofsky-Lansky score \< 60.
* Other condition deemed incompatible with inclusion in this study (estimated 2 year survival prognosis less than 25 %, expected poor protocol compliance, inability to swallow tablets, language difficulties).
* Inclusion in other study protocol precluding inclusion in this study.

Primary outcomes:
measure: Processing Speed Index (PSI)
timeFrame: 2 years after start of study treatment
Secondary outcomes:
measure: Fractional anisotropy (FA) index
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Other Wechsler Intelligence scale scores (except PSI):
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Grooved pegboard
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Beery/Buktenica visual motor integration (VMI)
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Conner´s Continous Performance Test (CPT) III
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Delis-Kaplan Executive Function System Trail Making Test (D-KEFS TMT)
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWT), age 8 years and above.
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Nepsy II: Inhibition, Verbal Fluency,
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Pediatric QoL Inventory (PedsQL)
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: University of California Los Angeles (UCLA) 3-Item Loneliness Scale (ULS-3)
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Strengths and Difficulties Questionnaire (SDQ)
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
measure: Behavior Rating Inventory of Executive Function (BRIEF).
timeFrame: Baseline (before treatment) - 5 years after start of study treatment
Other outcomes:
measure: Feasibility of recruitment and retention, numerical data
timeFrame: From screening - end of study (5 years)
measure: Feasibility of recruitment and retention, qualitative data
timeFrame: From screening - end of study (5 years)
measure: Feasibility of treatment - IMP treatment duration
timeFrame: During study treatment (appx 6 months)
measure: Feasibility of treatment - number of IMP reductions and stops
timeFrame: During study treatment (appx 6 months)
measure: Feasibility of treatment - reasons for IMP reductions and stops
timeFrame: During study treatment (appx 6 months)
measure: Feasibility of treatment - lithium serum concentration within target range
timeFrame: During study treatment (appx 6 months)
measure: Feasibility of treatment - adverse events
timeFrame: During study treatment (appx 6 months) + 1 month
Locations:
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset
state: Stockholm
city: Stockholm
country: Sweden
facility: HOPE
Study officials:
References: