Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

Cognitive Impairment Clinical Trial

— LiBRA  

Official title:

Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06051240
• Other study ID #: 2023-504071-24-00
• Secondary ID: 2023-504071-24-0
• Status: Recruiting
• Phase: Phase 2
• Start date: February 16, 2024
• Est. completion date: August 31, 2033

Study information

• Verified date: June 2023
• Source: Region Stockholm
• Contact: Klas Blomgren, MD, Professor
• Phone: 0046703233353
• Email: klas.blomgren[@]regionstockholm.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: August 31, 2033
• Est. primary completion date: August 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor
• Cognitive Decline
• Cognitive Dysfunction
• Cognitive Impairment
• Late Effect of Radiation
• Memory Impairment
• Radiotherapy Side Effect
• Radiotherapy; Complications

Intervention

Drug:
• Lithium
Lithium sulphate, 42 mg (6 mmol lithium)
• Placebo
White round tablet, 10 mm. Identical to experimental drug (lithium)

Locations

Country	Name	City	State
Sweden	Karolinska Universitetssjukhuset	Solna	Stockholm
Sweden	HOPE	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Region Stockholm	Rigshospitalet, Denmark

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Feasibility of recruitment and retention, numerical data	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)	From screening - end of study (5 years)
Other	Feasibility of recruitment and retention, qualitative data	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.	From screening - end of study (5 years)
Other	Feasibility of treatment - IMP treatment duration	Duration of IMP treatment, measured in total number of days where IMP was taken	During study treatment (appx 6 months)
Other	Feasibility of treatment - number of IMP reductions and stops	Numbers of IMP dose reductions; Number of IMP temporary stops	During study treatment (appx 6 months)
Other	Feasibility of treatment - reasons for IMP reductions and 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.	During study treatment (appx 6 months)
Other	Feasibility of treatment - lithium serum concentration within target range	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	During study treatment (appx 6 months)
Other	Feasibility of treatment - adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	During study treatment (appx 6 months) + 1 month
Primary	Processing Speed Index (PSI)	Cognitive processing speed. Normed score min 45, max 155. Higher = better.	2 years after start of study treatment
Secondary	Fractional anisotropy (FA) index	White matter integrity on MRI brain.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Other Wechsler Intelligence scale scores (except PSI):	Verbal Comprehension Index (VCI); Visual Spatial Index (VSI); Fluid Reasoning Index (FRI); Working Memory Index (WMI); Normed score min 45, max 155. Higher = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Grooved pegboard	Motor speed / manual dexterity. Unit: time in seconds to complete all pegs. Lower=better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Beery/Buktenica visual motor integration (VMI)	Visual motor integration. Normed score min 1, max 19. Higher = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Conner´s Continous Performance Test (CPT) III	Sustained attention. Multiple T-scores, min 0, max 80. Higher = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Delis-Kaplan Executive Function System Trail Making Test (D-KEFS TMT)	Executive function and inhibition, age 8 years and above. Normed score min 1, max 19. Higher = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWT), age 8 years and above.	Executive function and inhibition. Normed score min 1, max 19. Higher = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Nepsy II: Inhibition, Verbal Fluency,	Executive function and inhibition, age below 8 years. Normed score min 1, max 19. Higher = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Pediatric QoL Inventory (PedsQL)	Health related quality of life. Score min 0, max 100. Higher=better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	University of California Los Angeles (UCLA) 3-Item Loneliness Scale (ULS-3)	Loneliness scale. Score min 3, max 9. Lower = better.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Strengths and Difficulties Questionnaire (SDQ)	Psychosocial strengths and difficulties. Score min 0, max 40.	Baseline (before treatment) - 5 years after start of study treatment
Secondary	Behavior Rating Inventory of Executive Function (BRIEF).	Executive function. Score min 20, max 80.	Baseline (before treatment) - 5 years after start of study treatment