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NCT Number: NCT06051240

Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

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.

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Key information

Conditions

Cognitive Impairment Brain Diseases Brain Neoplasms Brain Tumor Central Nervous System Diseases Central Nervous System Neoplasms Cognition Disorders Cognitive Decline Cognitive Dysfunction Late Effect of Radiation Memory Disorders Memory Impairment Mental Disorders Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Neurobehavioral Manifestations Neurocognitive Disorders Neurologic Manifestations Pathological Conditions, Signs and Symptoms Radiation Injuries Radiotherapy Side Effect Radiotherapy; Complications Signs and Symptoms Wounds and Injuries

Age range

5 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Karolinska Universitetssjukhuset, Solna, Stockholm County, Sweden

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Lithium

Drug

Lithium sulphate, 42 mg (6 mmol lithium)

Other names: Lithionit, Lithium sulphate

Placebo

Drug

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

Primary outcomes

  1. Processing Speed Index (PSI)

    Time frame: 2 years after start of study treatment

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

Secondary outcomes

  1. Fractional anisotropy (FA) index

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

    White matter integrity on MRI brain.

  2. Other Wechsler Intelligence scale scores (except PSI):

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

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

  3. Grooved pegboard

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  4. Beery/Buktenica visual motor integration (VMI)

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  5. Conner´s Continous Performance Test (CPT) III

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  6. Delis-Kaplan Executive Function System Trail Making Test (D-KEFS TMT)

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  7. Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWT), age 8 years and above.

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  8. Nepsy II: Inhibition, Verbal Fluency,

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  9. Pediatric QoL Inventory (PedsQL)

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  10. University of California Los Angeles (UCLA) 3-Item Loneliness Scale (ULS-3)

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  11. Strengths and Difficulties Questionnaire (SDQ)

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

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

  12. Behavior Rating Inventory of Executive Function (BRIEF).

    Time frame: Baseline (before treatment) - 5 years after start of study treatment

    Executive function. Score min 20, max 80.

Other outcomes

  1. Feasibility of recruitment and retention, numerical data

    Time frame: From screening - end of study (5 years)

    • 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)

  2. Feasibility of recruitment and retention, qualitative data

    Time frame: From screening - end of study (5 years)

    • 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.

  3. Feasibility of treatment - IMP treatment duration

    Time frame: During study treatment (appx 6 months)

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

  4. Feasibility of treatment - number of IMP reductions and stops

    Time frame: During study treatment (appx 6 months)

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

  5. Feasibility of treatment - reasons for IMP reductions and stops

    Time frame: During study treatment (appx 6 months)

    • 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.

  6. Feasibility of treatment - lithium serum concentration within target range

    Time frame: During study treatment (appx 6 months)

    • 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

  7. Feasibility of treatment - adverse events

    Time frame: During study treatment (appx 6 months) + 1 month

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

Study contacts

Contact information is provided by the study sponsor or research team.

Gustaf Hellspong, MD, PhD Student

CONTACT

[email protected]

0707308144

Klas Blomgren, MD, Professor

CONTACT

[email protected]

0046703233353

Sponsors and collaborators

Lead sponsor

Region Stockholm

Other Gov

Collaborators

  • Rigshospitalet, Denmark

Registry information

Acronym: LiBRA

Important dates

Study start
2024
Primary completion
2030
Study completion
2033
First posted
Sep 22, 2023
Registry last updated
Apr 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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