Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

NCT06051240 | Recruiting Phase 2 DMC

• 1 other identifier: 2023-504071-24-00
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (1)

• Processing Speed Index (PSI)

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

  2 years after start of study treatment

Secondary Outcomes (12)

• Fractional anisotropy (FA) index

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

• Other Wechsler Intelligence scale scores (except PSI):

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

• Grooved pegboard

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

• Beery/Buktenica visual motor integration (VMI)

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

• Conner´s Continous Performance Test (CPT) III

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

Other Outcomes (7)

• Feasibility of recruitment and retention, numerical data

  From screening - end of study (5 years)

• Feasibility of recruitment and retention, qualitative data

  From screening - end of study (5 years)

• Feasibility of treatment - IMP treatment duration

  During study treatment (appx 6 months)

Study Arms (2)

Lithium

EXPERIMENTAL

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.

Drug: Lithium

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lithium DRUG

Lithium sulphate, 42 mg (6 mmol lithium)

Also known as: Lithionit, Lithium sulphate

Lithium

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Region Stockholm: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (2)

Karolinska Universitetssjukhuset

Solna, Stockholm County, 171 64, Sweden

NOT YET RECRUITING

HOPE

Stockholm, 17176, Sweden

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Radiation Injuries; Brain Neoplasms; Memory Disorders

Interventions

Lithium; lithium sulfate

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Wounds and Injuries; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Central Study Contacts

Klas Blomgren, MD, Professor

CONTACT

0046703233353; klas.blomgren@regionstockholm.se

Gustaf Hellspong, MD, PhD Student

CONTACT

0707308144; gustaf.hellspong@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical-looking placebo is used. S-lithium levels are masked by using a separate lab service and sham values for placebo group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 12, 2023
• First Posted: September 22, 2023
• Study Start: February 16, 2024
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2033
• Last Updated: April 12, 2024

Record last verified: 2023-06

Locations

SE (2)