Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

Phase 2

Recruiting

• Conditions: Cognitive Decline; Radiotherapy Side Effect; Brain Tumor; Late Effect of Radiation; Cognitive Impairment; Radiotherapy; Complications; Memory Impairment
• Interventions: Drug: Placebo; Drug: Lithium

• Registration Number: NCT06051240
• Lead Sponsor: Region Stockholm

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.

Study Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-06-12
• Study First Submitted QC: 2023-09-20
• Study First Posted: 2023-09-22
• Study Start: 2024-02-16
• Last Update Submitted: 2024-04-11
• Last Update Posted: 2024-04-12
• Primary Completion: 2030-08-31
• Study Completion: 2033-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 84

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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	Lithium	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.

Primary Outcome Measures

Name	Time	Method
Processing Speed Index (PSI)	2 years after start of study treatment	Cognitive processing speed. Normed score min 45, max 155. Higher = better.

Secondary Outcome Measures

Name	Time	Method
Grooved pegboard	Baseline (before treatment) - 5 years after start of study treatment	Motor speed / manual dexterity. Unit: time in seconds to complete all pegs. Lower=better.
Pediatric QoL Inventory (PedsQL)	Baseline (before treatment) - 5 years after start of study treatment	Health related quality of life. Score min 0, max 100. Higher=better.
Behavior Rating Inventory of Executive Function (BRIEF).	Baseline (before treatment) - 5 years after start of study treatment	Executive function. Score min 20, max 80.
Fractional anisotropy (FA) index	Baseline (before treatment) - 5 years after start of study treatment	White matter integrity on MRI brain.
Delis-Kaplan Executive Function System Trail Making Test (D-KEFS TMT)	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.
University of California Los Angeles (UCLA) 3-Item Loneliness Scale (ULS-3)	Baseline (before treatment) - 5 years after start of study treatment	Loneliness scale. Score min 3, max 9. Lower = better.
Other Wechsler Intelligence scale scores (except PSI):	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.
Conner´s Continous Performance Test (CPT) III	Baseline (before treatment) - 5 years after start of study treatment	Sustained attention. Multiple T-scores, min 0, max 80. Higher = better.
Nepsy II: Inhibition, Verbal Fluency,	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.
Strengths and Difficulties Questionnaire (SDQ)	Baseline (before treatment) - 5 years after start of study treatment	Psychosocial strengths and difficulties. Score min 0, max 40.
Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWT), age 8 years and above.	Baseline (before treatment) - 5 years after start of study treatment	Executive function and inhibition. Normed score min 1, max 19. Higher = better.
Beery/Buktenica visual motor integration (VMI)	Baseline (before treatment) - 5 years after start of study treatment	Visual motor integration. Normed score min 1, max 19. Higher = better.

Trial Locations

Locations (2)

Karolinska Universitetssjukhuset; 🇸🇪 Solna, Stockholm, Sweden

HOPE; 🇸🇪 Stockholm, Sweden