Cognitive ImpairmentPhase 2LiBRANCT06051240
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy
A Phase 2 study testing Lithium in people with Cognitive Impairment and Cognitive Decline, run by Region Stockholm at 2 sites in Sweden.
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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Cognitive Impairment, Cognitive Decline, Radiotherapy Side Effect
- What is being tested?
- Lithium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 2 sitesSweden
- Study dates
- 16 Feb 2024to 31 Aug 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden2 sites, 2 recruiting
- Not yet recruiting
Karolinska Universitetssjukhuset
Solna, Stockholm County, 171 64
Klas Blomgren, MD, Professor, 0046703233353, klas.blomgren@regionstockholm.se
Gustaf Hellspong, MD, PhD Student, 0046707308144, gustaf.hellspong@regionstockholm.se
- Recruiting
HOPE
Stockholm, 17176
Gustaf Hellspong, MD, +46812371594, gustaf.hellspong@regionstockholm.se
Klas Blomgren, MD, professor, +46703233353, klas.blomgren@regionstockholm.se
About this study
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.
Read the 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.
- Conditions
- Cognitive Impairment, Cognitive Decline, Radiotherapy Side Effect, Radiotherapy; Complications, Brain Tumor, Memory Impairment
- Being tested
- Lithium, Placebo
- Keywords
- lithium, neuroprotection, neuroprotective, regenerative, prevention, radiation, pediatric brain tumor, brain tumor, cognition, cognitive
- Medical subject headings
- Cognitive Dysfunction, Radiation Injuries, Brain Neoplasms, Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Also called Lithionit, Lithium sulphate
Lithium sulphate, 42 mg (6 mmol lithium)
PlaceboDrug
White round tablet, 10 mm. Identical to experimental drug (lithium)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Processing Speed Index (PSI)
Cognitive processing speed. Normed score min 45, max 155. Higher = better.
Measured: 2 years after start of study treatment
Secondary outcomes (12)
Fractional anisotropy (FA) index
White matter integrity on MRI brain.
Measured: Baseline (before treatment) - 5 years after start of study treatment
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (before treatment) - 5 years after start of study treatment
Strengths and Difficulties Questionnaire (SDQ)
Psychosocial strengths and difficulties. Score min 0, max 40.
Measured: Baseline (before treatment) - 5 years after start of study treatment
Behavior Rating Inventory of Executive Function (BRIEF).
Executive function. Score min 20, max 80.
Measured: Baseline (before treatment) - 5 years after start of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2023
- Study start16 Feb 2024
- Primary completion31 Aug 2030 (estimated)
- Study completion31 Aug 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Region StockholmThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Stockholm
- Sponsor type
- Other government
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06051240
- Sponsor's protocol ID
- 2023-504071-24-00
- Other IDs
- 2023-504071-24-00, 2023
- Acronym
- LiBRA
- Status last verified
- Jun 2023
- First submitted
- 12 Jun 2023
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy
- ClinicalTrials.gov ID
- NCT06051240
- Acronym / sponsor ID
- LiBRA / 2023-504071-24-00
- Conditions
- Cognitive Impairment, Cognitive Decline, Radiotherapy Side Effect, Radiotherapy; Complications, Brain Tumor, Memory Impairment
- Keywords
- lithium, neuroprotection, neuroprotective, regenerative, prevention, radiation, pediatric brain tumor, brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Region StockholmOther government
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- 16 Feb 2024 (actual)
- Primary completion
- 31 Aug 2030 (estimated)
- Study completion
- 31 Aug 2033 (estimated)
- First posted
- 22 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Lithium | Experimental | Drug: LithiumLithionit 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 | Drug: PlaceboIdentical 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. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LithiumAlso: Lithionit, Lithium sulphateLithium sulphate, 42 mg (6 mmol lithium) | Drug | Lithium |
| PlaceboWhite round tablet, 10 mm. Identical to experimental drug (lithium) | Drug | Placebo |
Primary outcome
Processing Speed Index (PSI)
Time frame: 2 years after start of study treatment
Cognitive processing speed. Normed score min 45, max 155. Higher = better.
12 secondary outcomes
Fractional anisotropy (FA) index
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Other Wechsler Intelligence scale scores (except PSI):
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Grooved pegboard
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Beery/Buktenica visual motor integration (VMI)
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Conner´s Continous Performance Test (CPT) III
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Delis-Kaplan Executive Function System Trail Making Test (D-KEFS TMT)
Time frame: 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.
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Nepsy II: Inhibition, Verbal Fluency,
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Pediatric QoL Inventory (PedsQL)
Time frame: Baseline (before treatment) - 5 years after start of study treatment
University of California Los Angeles (UCLA) 3-Item Loneliness Scale (ULS-3)
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Strengths and Difficulties Questionnaire (SDQ)
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Behavior Rating Inventory of Executive Function (BRIEF).
Time frame: Baseline (before treatment) - 5 years after start of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lithium in people with Cognitive Impairment and Cognitive Decline, run by Region Stockholm at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Klas Blomgren, MD, Professor (0046703233353, klas.blomgren@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Processing Speed Index (PSI) (time frame: 2 years after start of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.