The LiLa-Bipolar RCT

2023-509607-32-00 Therapeutic use (Phase IV) Ongoing, recruiting

Start 29 Apr 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 200
Countries 1
Sites 1

Bipolar Disorder, Type II

Lithium versus Lamotrigine in bipolar disorder, type II – a single blinded randomized controlled trial (the LiLa-Bipolar RCT). To conduct a 6-month RCT comparing effects of lithium versus lamotrigine on mood stabilization and other critical patient outcomes in patients with BDII and to test whether principal effects ar…

Key facts

Sponsor
Region Hovedstaden, Frederiksberg Hospital
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Psychiatry and Psychology [F] - Mental Disorders [F03]
Trial duration
29 Apr 2024 → ongoing
Decision date (initial)
2024-03-25
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2023-509607-32-00
WHO UTN
U1111-1300-4501

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy, Efficacy

Lithium versus Lamotrigine in bipolar disorder, type II – a single blinded randomized controlled trial (the LiLa-Bipolar RCT).
To conduct a 6-month RCT comparing effects of lithium versus lamotrigine on mood stabilization and other critical patient outcomes in patients with BDII and to test whether principal effects are antimanic, antidepressant and/or prophylactic against relapse.
Primary hypothesis: Lithium improves mood stabilization compared with lamotrigine.

Secondary objectives 3

  1. Secondary: Lithium decreases depression and hypomania and improves functioning and cognition compared with lamotrigine.
  2. Tertiary: Mood stabilization is higher in patients with hsCRP values > 3 mg/l at inclusion in patients treated with lithium compared with lamotrigine.
  3. Quaternary: Baseline (before randomization) inflammatory marker levels (hair cortisol and cytokines in blood samples) are lowered in the lithium treatment group after 6 months compared with the lamotrigine treatment group.

Conditions and MedDRA coding

Bipolar Disorder, Type II

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. All patients referred to the clinic as newly diagnosed with BDII will routinely be asked for inclusion in the RCT. Patients are included during 1) depressive state, 2) hypomanic state or 3) full or partial remission.
  2. Bipolar disorder, type II with diagnoses confirmed by SCAN interview
  3. Age 18-70 years
  4. Speaks and writes Danish or English at a level equal to mother tongue
  5. Habile (i.e., able to give informed consent)

Exclusion criteria 6

  1. Past non-response or intolerance to lamotrigine or lithium with > 6 weeks treatment at an adequate dosage
  2. Currently taking mod stabilizers at enrollment in CADIC
  3. Chronic kidney disease with GFR 0-10 ml/min
  4. Severe cardiac insufficiency (NYHA IIIb-IV)
  5. Brugadas syndrome
  6. Severe hypothyroidism despite treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Primary: Mood stabilization will be measured by a mood instability score reflecting the daily variability in self-monitored mood collected via the Monsenso system (see section 2.3.4 in Protocol).

Secondary endpoints 1

  1. Young mania rating scale, Hamilton Rating Scale for Depression (17 items), functional assessment short test, Internet-based Cognition Assessment Tool (ICAT), blood based inflammation markers collected in blood sample, hair cortisol level (see detailed description in section 4 in protocol).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Litiumkarbonat "OBA", filmovertrukne tabletter

PRD1713040 · Product

Active substance
Lithium Carbonate
Pharmaceutical form
FILM COATED TABLET
Route of administration
ORAL
Max daily dose
0.8 mmol/l millimole(s)/litre
Max total dose
0.8 mmol/l millimole(s)/litre
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
N05AN01 — LITHIUM
Marketing authorisation
7310
MA holder
OBA-PHARMA APS
MA country
Denmark
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Lamictal 25 mg tablete

PRD2459328 · Product

Active substance
Lamotrigine
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
400 mg milligram(s)
Max total dose
146000 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
N03AX09 — LAMOTRIGINE
Marketing authorisation
H/96/00871/057
MA holder
GLAXOSMITHKLINE TRADING SERVICES LIMITED
MA country
Slovenia
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

38 Total trials 23 Recruiting 7 Ended
Academic / Non-commercial
Sponsor organisation
Region Hovedstaden
Address
Esther Ammundsens Vej 36
City
Copenhagen Nv
Postcode
2400
Country
Denmark

Scientific contact point

Organisation
Psykiatrisk Center Kobenhavn
Contact name
Lars Vedel Kessing

Public contact point

Organisation
Psykiatrisk Center Kobenhavn
Contact name
PCK

Third parties 1

OrganisationCity, countryDuties
Frederiksberg Hospital
ORG-100028217
 Frederiksberg, Denmark On site monitoring

Frederiksberg Hospital

5 Total trials 3 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Frederiksberg Hospital
Address
Nordre Fasanvej 57, 1st Floor Entrance 2 1st Floor Entrance 2
City
Frederiksberg
Postcode
2000
Country
Denmark

Public contact point

Organisation
Psykiatrisk Center Kobenhavn
Contact name
PCK

Third parties 1

OrganisationCity, countryDuties
Frederiksberg Hospital
ORG-100028217
 Frederiksberg, Denmark On site monitoring

Sponsor responsibilities

Article 77 compliance
Region Hovedstaden
Contact point sponsor
Region Hovedstaden
Article 77 implementation
Region Hovedstaden

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruiting 200 1
Rest of world — 0 —

Investigational sites

Denmark

1 site · Ongoing, recruiting
Psykiatrisk Center Kobenhavn
Copenhagen Affective Disorder Clinic (CADIC), Esther Ammundsens Vej 36, 2400, Copenhagen Nv

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2024-04-29 2024-05-08

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_ MARS Adherence 1
Protocol (for publication) D1_ChildhoodTQ 1
Protocol (for publication) D1_COBRA_danskversion 1
Protocol (for publication) D1_Cohens_pss-skala_danskvalideretversion 1
Protocol (for publication) D1_CRS 1
Protocol (for publication) D1_CSFQ-F 1
Protocol (for publication) D1_CSFQ-M 1
Protocol (for publication) D1_FAST_Dansk 1
Protocol (for publication) D1_Hamilton depressionsskale D-17 interview guide 1
Protocol (for publication) D1_HAMILTON-DEPRESSION_17 1
Protocol (for publication) D1_IPAQ 1
Protocol (for publication) D1_LiLaprotocol_2023-509607-32-00 6
Protocol (for publication) D1_Monsenso_screenshots 2
Protocol (for publication) D1_MSCQ 1
Protocol (for publication) D1_Perceived Stress Scale 1
Protocol (for publication) D1_Pittsburgh Sleep Quality Index 1
Protocol (for publication) D1_SCIP_SKEMA_2_T6_dansk 1
Protocol (for publication) D1_SCIP_SKEMA_3_T0_dansk 1
Protocol (for publication) D1_UKU s Bivirkningsskala Skala Til Registering af Unskede Virkninger af Psykofarmaka 1
Protocol (for publication) D1_WHO5 trivselsskema dansk version 1
Protocol (for publication) D1_WHOQOL 1
Protocol (for publication) D1_YMRS 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_lamictal 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_lithiumkarbonat 1
Synopsis of the protocol (for publication) D1_Protocol_synopsis_2023-509607-32-00 1

Application history

7 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-12-01 Denmark Acceptable
2024-03-22
 2024-03-25
2 SUBSTANTIAL MODIFICATION SM-1 2024-04-02 Denmark Acceptable 2024-04-05
3 NON SUBSTANTIAL MODIFICATION NSM-4 2024-04-29 Denmark Acceptable 2024-04-29
4 SUBSTANTIAL MODIFICATION SM-2 2024-06-17 Denmark Acceptable
2024-09-02
 2024-09-02
5 SUBSTANTIAL MODIFICATION SM-3 2025-03-06 Denmark Acceptable
2025-03-10
 2025-03-10
6 NON SUBSTANTIAL MODIFICATION NSM-6 2026-03-03 Acceptable
2025-03-10
7 NON SUBSTANTIAL MODIFICATION NSM-8 2026-03-10 Denmark Acceptable
2025-03-10
 2026-03-10