An interventional study of Cognitive assessment of obsessive-compulsive and impulsive behaviours and Genomic analysis in Romano-Ward Syndrome, Long QT Syndrome and Compulsive Behavior, sponsored by Biotrial. Status unknown at 2 sites in France. Open to participants aged 18 Years to 48 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-01-20.
Sponsored by Biotrial · Not applicable, Interventional, and Basic science
The objectives of the study are to investigate if KCNQ1 mutation in Romano-Ward long QT patients can be associated with changes in insulin regulation and with psychological features of compulsivity, impulsivity and behavioural rigidity.
Romano-Ward Syndrome (RWS) is a rare disorder characterized by prolongation of the QT interval, as well as T-wave abnormalities and possibly polymorphic ventricular fibrillation. RWS is inherited in an autosomal dominant fashion. Mutations in the potassium voltage-gated channel subfamily Q Member 1 (KCNQ1), potassium voltage-gated channel subfamily H member 2 (KCNH2), sodium voltage-gated channel alpha subunit 5 (SCN5A), potassium voltage-gated channel subfamily E regulatory subunit 1 (KCNE1), and potassium voltage-gated channel subfamily E regulatory subunit 2 (KCNE2) genes are known to be causative, and these five genes together are responsible for virtually 100% of cases of RWS.
Dysregulation of insulin signalling has been implicated in multimorbidity across the lifespan, in particular in type 2 diabetes, metabolic syndrome, obesity and RWS. Numerous studies have shown a relationship between RWS and hyperinsulinemia. More recently, altered insulin signalling has also been implicated in neurodegenerative brain disorders, dementias and Alzheimer's disease. Diseases characterized by dysregulation of insulin signalling (i.e. insulinopathies) present a major health, societal, and economic burden. These insulin signalling-associated diseases are mostly chronic, and with limited or absent curative treatments. At the current time, the recognition and clinical management of insulin comorbidity remains poorly established; brain-based comorbidity is generally neglected, and medical efforts are only devoted to the management of the primary, somatic diagnosis.
The present study will be a part of the European Union (EU)-funded PRIME (for Prevention and Remediation of Insulin Multimorbidity in Europe) research program, which primary goal is to identify and specify the molecular mechanisms underlying the insulin multimorbidities through investigation of the diseases that cause the highest burden and costs to patients and society, and to outline new directions for research and clinical care thereof. The primary hypothesis of the PRIME project is that comorbidity observed in these somatic diseases (DM2, metabolic syndrome, obesity, RWS) is a result of dysregulated central and peripheral insulin signalling, downstream of synaptic dysfunction and of learning, memory, and executive functions impairments. This non-competitive EU Horizon2020 project will study the role of KCNQ1, a key molecule in insulin regulation, in the insulinopathies across different levels of organismal organisation.
The study will include 50 KCNQ1-mutated subjects (mainly RWS patients but also subjects carrying the KCNQ1 mutation but without phenotypic manifestation of long QT syndrome, and, because of the strong interest of the PRIME project in genetic analyses, family relatives carrying the same KCNQ1 mutation) and 50 matched healthy subjects. By comparing the test population to healthy subjects, the main objective of the trial is to test the hypothesis of an involvement of KCNQ1 in compulsivity, impulsivity and cognitive rigidity.
The insulin regulation evaluations will be performed by measuring glucose, insulin and glycated haemoglobin (HbA1c) in subjects. Compulsivity, impulsivity and behavioural rigidity will be assessed using 4 neuropsychological questionnaires (OCI-R, ASBQ, UPPS-P, CHIRP) and one objective test, the CPT.
Moreover, DNA extraction will be performed in order to search for associations between mutations, insulin regulation and psychological features in conducting a Genome-Wide Association Study (GWAS) (exploratory objective).
101 studies on the registry are indexed under Long QT Syndrome; 20 are open to participants now.
This study's planned enrollment of 100 is above the median of 45 across 46 interventional studies indexed under Long QT Syndrome.
Browse Long QT Syndrome studies →This is the only study on the registry with Biotrial as lead sponsor.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This arm includes : * KCNQ1-mutated subjects with long QT Romano-Ward syndrome * KCNQ1-mutated subjects without phenotypic expression of the Romano-Ward syndrome * family relatives of a KCNQ1-mutated enrolled subject, carrying the KCNQ1 family mutation
Behavioral: Cognitive assessment of obsessive-compulsive and impulsive behaviours · Genetic: Genomic analysis · Diagnostic Test: Glucoregulation assessment
Healthy subjects will be matched to KCNQ1 subjects. The matching factors will be age per decade (18-28 years, \> 28-38 years, \> 38-48 years), gender and body mass index (BMI: ≤ 24.9 kg/m2; 25-29.9 kg/m2; \> 30 kg/m2).
Behavioral: Cognitive assessment of obsessive-compulsive and impulsive behaviours · Genetic: Genomic analysis · Diagnostic Test: Glucoregulation assessment
The content of the assessment will be the same for all subjects and will consist of a cognitive assessment (attention, impulsivity) and a clinical assessment (impulsive behaviour, autistic traits,obsessive-compulsive behaviour).
A genome-wide association study (GWAS) will be performed for all subjects to search for associations between KCNQ1 mutations, insulin regulation and psychological features.
Fasted glycaemia and insulinaemia, glycated haemoglobin (HbA1c) and glycaemia following an oral glucose challenge test will be measured in all study subjects.
Outcome related to glucoregulation : fasted glycemia
Plasma glucose concentration
Time frame: 15 minutes
Outcome related to glucoregulation : fasted insulin levels
Plasma insulin concentration
Time frame: 15 minutes
Outcome related to glucoregulation : glycated haemoglobin (HbA1c)
Blood HbA1c concentration
Time frame: 15 minutes
Outcome related to glucoregulation : glycemia 2hours following an oral glucose challenge
Plasma glucose concentration
Time frame: 2 hours
Obsessive Compulsive Inventory-Revised (OCI-R) questionnaire total score and subscale scores
Subscales of OCI-R: washing, obsessing, hoarding, ordering, checking, neutralising
Time frame: 30 minutes
Adult Social Behaviour Questionnaire (ASBQ) total score and subscale scores
Subscales of ASBQ : reduced contacts, reduced empathy, reduced interpersonal insight, violations of social conventions, insistence of sameness, sensory stimulation and motor stereotypies.
Time frame: 30 minutes
Urgency, Premeditation, Perseverance, Sensation seeking, and Positive urgency scale (UPPS-P) subscale scores
Subscales of UPPS-P: negative urgency, lack of premeditation, lack of perseverance, sensation-seeking, positive urgency
Time frame: 30 minutes
Childhood Retrospective Perfectionism Questionnaire (CHIRP) total score
Total score
Time frame: 30 minutes
Continuous Performance Task (CPT)
Variables of the CPT : omission errors, commission errors/false alarms, hits, hit rate, hit reaction time, difference between hit rate and false alarms rate (d').
Time frame: 1 hour
Genomic analyses (GWAS)
DNA methylation status at the KCNQ1 locus and Polygenic Risk Scores (PRS)
Time frame: 15 minutes
Plan to share: Yes — All anonymized individual participant data will be shared within the PRIME consortium collaborators in accordance with the PRIME Consortium Agreement
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Individual participant data will be available starting in january 2023 and until december 2025
Started Jan 2021 (actual). Primary completion is estimated for Dec 2021, 11 months after the start.
Of 15 interventional studies with no phase under Long QT Syndrome, half reached primary completion within 18 months of starting (the median), counting those still running; a quarter within 6 and three quarters within 28. This study's planned 11 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.
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