Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
114
Countries
2
Sites
10
Brain tumor
To assess the efficacy of lithium treatment in preventing late-appearing cognitive processing speed impairment in children after brain radiotherapy for a CNS malignancy.
Key facts
- Sponsor
- Karolinska University Hospital
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 7 Nov 2023 → ongoing
- Decision date (initial)
- 2024-05-22
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Karolinska Universitetssjukhuset
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To assess the efficacy of lithium treatment in preventing late-appearing cognitive processing speed impairment in children after brain radiotherapy for a CNS malignancy.
Secondary objectives 3
- To assess the efficacy of lithium treatment through evaluation of other neuropsychological and quality of life test scores.
- To assess the effect of lithium treatment on radiological outcomes.
- To explore the safety, tolerability and feasibility of lithium treatment.
Conditions and MedDRA coding
Brain tumor
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Age equal or above 5 years.
- Age less than 18 years at time of radiotherapy
- Has received cranial/craniospinal radiation treatment of brain tumor within the last 4 years.
- Adequate contraception 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 therafter.
- Written informed consent from participant and/or legal guardians.
Exclusion criteria 10
- Allergy/hypersensitivity to lithium or any of the excipients
- Renal failure (Cystatin C derived GFR < 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 conditions deemed incompatible with inclusion in this study (should be discussed with PI). This can include, but is not restricted to: o Estimated 2-year survival prognosis less than 25 %. o Serious psychiatric condition and/or suicidal thoughts. o Expected poor protocol compliance. o Language difficulties.
- Ongoing antitumoral therapy.
- Inclusion in another study protocol precluding inclusion in this study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change in Processing Speed Index (PSI) test score (sub-test of WPPSI/WISC/WAIS) 2 years after the start of study treatment compared to baseline, before study treatment.
Secondary endpoints 12
- Changes in the following neuropsychological/other test scores: • Complete set of WPPSI-IV/WISC-V/WAIS-IV sub-tests and their associated indices: o Processing Speed Index (PSI) o Verbal Comprehension Index (VCI) o Visual Spatial Index (VSI) o Fluid Reasoning Index (FRI) o Working Memory Index (WMI)
- Changes in Grooved Pegboard (motor speed)
- Changes in Beery/Buktenica VMI (visual-motor integration)
- Changes in Conner´s CPT III (sustained attention)
- Changes in D-KEFS TMT, D-KEFS CWT, D-KEFS Verbal fluency (executive functions) o If age <8 years: Nepsy II: Inhibition, Verbal fluency
- Changes in Nepsy Word list (memory)
- Changes in Pediatric Quality of Life (PedsQL) Generic Core Scale Standard, Multidimensional Fatigue Scale.
- Changes in UCLA Loneliness Rating Scale 3 (ULS-3)
- Changes in Strengths and Difficulties Questionnaire (SDQ)
- Changes in Behavior Rating Inventory of Executive Function (BRIEF)
- Changes in the following neuropsychological/other test scores: o Processing Speed Index (PSI) o Working Memory Index (WMI)
- Evaluation of volumetric measures (hippocampal, total gray matter and total white matter volume) and diffusion tensor imaging (DTI) indices (FA, MD, RD, AD) on brain MRI at 6 months, 1 year, 2 years, 5 years and 10 years after start of study treatment, compared to baseline.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Lithionit 42 mg (6 mmol) depottablett
PRD369552 · Product
- Active substance
- Lithium Sulphate, Anhydrous
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 336 mg milligram(s)
- Max total dose
- 60 g gram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- N05AN01 — LITHIUM
- Marketing authorisation
- 13525
- MA holder
- KARO PHARMA AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Placebo Matching 42MG Lithionit, 10MM, White, Round Tablets
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Karolinska University Hospital
- Sponsor organisation
- Karolinska University Hospital
- Address
- Eugeniavagen 3
- City
- Solna
- Postcode
- 171 64
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Klas Blomgren
Public contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Klas Blomgren
Locations
2 EU/EEA countries · 10 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 30 | 4 |
| Sweden | Ongoing, recruiting | 84 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Aarhus Universitetshospital
Department of Paediatrics and Adolescent Medicine, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Aalborg University Hospital
Department of Paediatrics and Adoelscent Medicine, Reberbansgade 15, 9000, Aalborg
Rigshospitalet
Department of Paediatrics and Adolescent Medicine, Blegdamsvej 9, 2100, Copenhagen Oe
Odense University Hospital
Department of Paediatrics and Adolescent Medicine, J B Winsloews Vej 4, 5000, Odense C
University Hospital Of Northern Sweden
Pediatric hematology and oncology, University Hospital, 901 85, Umeaa
Region Oestergoetland
BOND Oncology, Universitetssjukhuset I, 58185, Linkoping
Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
Center for pediatric oncology, Behandlingsvagen 7, Harlanda, Gothenburg
Region Skane Skanes Universitetssjukhus
Center for pediatric oncology, Entregatan 7, 222 42, Lund
Uppsala University Hospital
Pediatric hematology and oncology, Akademiska Sjukhuset, 751 85, Uppsala
Karolinska University Hospital
Dept. of Women’s and Children’s Health, Eugeniavagen 3, 171 64, Solna
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2025-07-30 | 2026-01-06 | |||
| Sweden | 2023-11-07 | 2023-11-07 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 77 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | APPENDIX II Dose Schedule LiBRA | 1 |
| Protocol (for publication) | LiBRA Study protocol Summary of changes v 1_2 vs 2_0 | 2.0 |
| Protocol (for publication) | LiBRA Study protocol Summary of changes v 2_0 vs v 2_1 | 2.1 |
| Protocol (for publication) | LiBRA Study Protocol_TC | 2.1 |
| Protocol (for publication) | Trial protocol LiBRA | 2.1 |
| Recruitment arrangements (for publication) | forfarande-for-rekrytering-och-samtyckesprocess_LiBRA_20230216_KB_GH | 1 |
| Recruitment arrangements (for publication) | Informed Consent - Patient Recruitment Procedure DK | 2 |
| Recruitment arrangements (for publication) | LiBRA - Informed Consent - Patient Recruitment Procedure DK TC | 2 |
| Subject information and informed consent form (for publication) | Appendix A_30JUN2025_ENG | 2.0 |
| Subject information and informed consent form (for publication) | APPENDIX II Dose Schedule LiBRA | 1 |
| Subject information and informed consent form (for publication) | APPENDIX III_LiBra_PATIENTKORT_15APR2023 | 1 |
| Subject information and informed consent form (for publication) | Bilag A - Studieschema Dansk | 2.0 |
| Subject information and informed consent form (for publication) | Bilag A - Studieskema_DK_TC | 2.0 |
| Subject information and informed consent form (for publication) | Bilaga A_17APR2023 | 2.0 |
| Subject information and informed consent form (for publication) | Bilaga A_TC | 2.0 |
| Subject information and informed consent form (for publication) | BRIEF 11-17 ar | 1 |
| Subject information and informed consent form (for publication) | BRIEF fran 18 ar | 1 |
| Subject information and informed consent form (for publication) | BRIEF-2 Foraldrar | 1 |
| Subject information and informed consent form (for publication) | BRIEF-2 forldre | 1 |
| Subject information and informed consent form (for publication) | BRIEF-A Self Danish 18-90 ar | 1 |
| Subject information and informed consent form (for publication) | BRIEF-SR 11-18 ar | 1 |
| Subject information and informed consent form (for publication) | Deltagareinformation Vardnadshavare | 2.0 |
| Subject information and informed consent form (for publication) | Initially submitted LiBRA deltagerinformation forldre Clean | 1 |
| Subject information and informed consent form (for publication) | LiBRA Brev Pre-screening | 1 |
| Subject information and informed consent form (for publication) | LiBRA Brev Pre-screening_DK | 1 |
| Subject information and informed consent form (for publication) | LiBRA Deltagerinformation 10-14 ar Clean | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation 10-14 ar_TC | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation 15-17 ar | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation 15-17 ar TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA Deltagerinformation 5-9 ar Clean | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation 5-9 ar_TC | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation forldre | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation forldre TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation over 18 ar | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA deltagerinformation over 18 ar TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA Letter Pre-screening_ENG | 1 |
| Subject information and informed consent form (for publication) | LiBRA Medicindagbog | 1.0 |
| Subject information and informed consent form (for publication) | LiBRA patientkort | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA Patientkort_DK_TC | 2 |
| Subject information and informed consent form (for publication) | LiBRA PIS-ICF 10-14 years ENG | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA PIS-ICF 15-17 years ENG | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA PIS-ICF 18 years ENG | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA PIS-ICF 5-9 years ENG | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA PIS-ICF Parents ENG | 2.0 |
| Subject information and informed consent form (for publication) | LIBRA_Deltagareinformation Vardnadshavare_TC | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_ICF_10-14 ar | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_ICF_10-14 ar_TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_ICF_15-17 ar | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_ICF_15-17 ar_TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_ICF_5-9 ar | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_ICF_5-9 ar_TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_Vuxna | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_Deltagareinformation_Vuxna_TC | 2.1 |
| Subject information and informed consent form (for publication) | LiBRA_ICF_10-14 yrs_ENG_TC | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA_ICF_15-17 yrs_ENG_TC | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA_ICF_5-9 yrs_ENG_TC | 2.0 |
| Subject information and informed consent form (for publication) | LiBRA_ICF_Adults_ENG_TC | 2.0 |
| Subject information and informed consent form (for publication) | LIBRA_ICF_Parents_ENG_TC | 2.0 |
| Subject information and informed consent form (for publication) | PedsQL-3_0-Fatigue-All_AU3_0_swe-SE | 3.0 |
| Subject information and informed consent form (for publication) | PedsQL-3-0-Fatigue-All_AU3-0_dan-DK | 3.0 |
| Subject information and informed consent form (for publication) | PedsQL-4_0-Core-All_AU4_0_swe-SE | 4.0 |
| Subject information and informed consent form (for publication) | PedsQL-4-0-Core-All_AU4-0_dan-DK | 4.0 |
| Subject information and informed consent form (for publication) | SDQ Dansk | 1 |
| Subject information and informed consent form (for publication) | SDQ_Danish_pt11-17single | 1 |
| Subject information and informed consent form (for publication) | SDQ_Danish_pt4-10single | 1 |
| Subject information and informed consent form (for publication) | SDQ_Danish_s11-17single | 1 |
| Subject information and informed consent form (for publication) | SDQ_Danish_sOver17single | 1 |
| Subject information and informed consent form (for publication) | SDQ_SE_L4-17full | 1 |
| Subject information and informed consent form (for publication) | SDQ_SE_p4-17full | 1 |
| Subject information and informed consent form (for publication) | SDQ_SE_pt4-17single | 1 |
| Subject information and informed consent form (for publication) | SDQ_SE_s11-17single | 1 |
| Subject information and informed consent form (for publication) | SDQ_SE_s17plus_full | 1 |
| Subject information and informed consent form (for publication) | ULS Dansk | 1 |
| Subject information and informed consent form (for publication) | ULS-3 SE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Lithionit_SmPC_22JUL2020 | 1 |
| Synopsis of the protocol (for publication) | LiBRA_Protokollsammanfattning SE | 2.0 |
| Synopsis of the protocol (for publication) | LiBRA_Protokollsammanfattning_TC | 2.0 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-02-22 | Sweden | Acceptable 2023-05-02
|
2023-05-02 |
| 2 | SUBSEQUENT ADDITION OF MSC | APP-2 | 2024-02-26 | 2024-05-22 | ||
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-11-11 | 2024-11-11 | ||
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-07-15 | Sweden | Acceptable 2025-09-24
|
2025-09-24 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-10-06 | Sweden | Acceptable 2025-09-24
|
2025-10-06 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2026-05-20 | Sweden | Acceptable 2025-09-24
|
2026-05-20 |