Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2023-504071-24-00 | Other Identifier | EudraCT |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Rigshospitalet, Denmark | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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:
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lithium | Drug | Lithium sulphate, 42 mg (6 mmol lithium) |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Processing Speed Index (PSI) | Cognitive processing speed. Normed score min 45, max 155. Higher = better. | 2 years after start of study treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Fractional anisotropy (FA) index | White matter integrity on MRI brain. | Baseline (before treatment) - 5 years after start of study treatment |
| Other Wechsler Intelligence scale scores (except PSI): |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of recruitment and retention, numerical data |
| From screening - end of study (5 years) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Klas Blomgren, MD, Professor | Contact | 0046703233353 | klas.blomgren@regionstockholm.se | |
| Gustaf Hellspong, MD, PhD Student | Contact | 0707308144 | gustaf.hellspong@regionstockholm.se |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska Universitetssjukhuset | Not yet recruiting | Solna | Stockholm County | 171 64 | Sweden |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D011832 | Radiation Injuries |
| D001932 | Brain Neoplasms |
| D008569 | Memory Disorders |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D014947 | Wounds and Injuries |
Not provided
Not provided
| ID | Term |
|---|---|
| D008094 | Lithium |
| C054097 | lithium sulfate |
| ID | Term |
|---|---|
| D008672 | Metals, Alkali |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D019565 | Metals, Light |
Not provided
Not provided
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.
Not provided
Not provided
Identical-looking placebo is used. S-lithium levels are masked by using a separate lab service and sham values for placebo group.
| Placebo | Drug | White round tablet, 10 mm. Identical to experimental drug (lithium) |
|
Normed score min 45, max 155. Higher = better.
| Baseline (before treatment) - 5 years after start of study treatment |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Strengths and Difficulties Questionnaire (SDQ) | Psychosocial strengths and difficulties. Score min 0, max 40. | Baseline (before treatment) - 5 years after start of study treatment |
| Behavior Rating Inventory of Executive Function (BRIEF). | Executive function. Score min 20, max 80. | Baseline (before treatment) - 5 years after start of study treatment |
| Feasibility of recruitment and retention, qualitative data |
| From screening - end of study (5 years) |
| 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) |
| Feasibility of treatment - number of IMP reductions and stops |
| During study treatment (appx 6 months) |
| Feasibility of treatment - reasons for IMP reductions and stops |
| During study treatment (appx 6 months) |
| Feasibility of treatment - lithium serum concentration within target range |
| During study treatment (appx 6 months) |
| 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 |
| HOPE | Recruiting | Stockholm | 17176 | Sweden |
|
| D016543 |
| Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008670 |
| Metals |