Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy (LiBRA)

Region Stockholm

Status and phase: Enrolling; Phase 2

Conditions: Radiotherapy Side Effect; Late Effect of Radiation; Cognitive Impairment; Brain Tumor; Radiotherapy; Complications; Cognitive Decline; Memory Impairment

Treatments: Drug: Lithium; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06051240

2023-504071-24-00 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 estimated patients

Sex: All

Ages: 5+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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84 participants in 2 patient groups, including a placebo group

Lithium

Experimental group

Description:

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.

Treatment:

Drug: Lithium

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo