Evaluation of the Effects of KCNQ1 Mutation on Insulin Tolerance and Obsessive Compulsive Features in Long QT Romano-Ward Syndrome Patients.

NCT04715256 | Unknown

• 2 other identifiers: 2020-A02099-30847879
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Romano-Ward Syndrome; Long QT Syndrome; Compulsive Behavior; Healthy Individuals

Keywords

Romano-Ward Syndrome; Long QT Syndrome; Insulin-related diseases; Compulsive Behavior; ASBQ; CHIRP; OCI-R; UPPS-P; CPT; GWAS; Healthy individuals; KCNQ1 mutations

Outcome Measures

Primary Outcomes (4)

• Outcome related to glucoregulation : fasted glycemia

  Plasma glucose concentration

  15 minutes

• Outcome related to glucoregulation : fasted insulin levels

  Plasma insulin concentration

  15 minutes

• Outcome related to glucoregulation : glycated haemoglobin (HbA1c)

  Blood HbA1c concentration

  15 minutes

• Outcome related to glucoregulation : glycemia 2hours following an oral glucose challenge

  Plasma glucose concentration

  2 hours

Secondary Outcomes (5)

• Obsessive Compulsive Inventory-Revised (OCI-R) questionnaire total score and subscale scores

  30 minutes

• Adult Social Behaviour Questionnaire (ASBQ) total score and subscale scores

  30 minutes

• Urgency, Premeditation, Perseverance, Sensation seeking, and Positive urgency scale (UPPS-P) subscale scores

  30 minutes

• Childhood Retrospective Perfectionism Questionnaire (CHIRP) total score

  30 minutes

• Continuous Performance Task (CPT)

  1 hour

Other Outcomes (1)

• Genomic analyses (GWAS)

  15 minutes

Study Arms (2)

KCNQ1 mutated subjects

EXPERIMENTAL

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

SHAM COMPARATOR

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

Interventions

Cognitive assessment of obsessive-compulsive and impulsive behaviours BEHAVIORAL

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).

Healthy subjects; KCNQ1 mutated subjects

Genomic analysis GENETIC

A genome-wide association study (GWAS) will be performed for all subjects to search for associations between KCNQ1 mutations, insulin regulation and psychological features.

Healthy subjects; KCNQ1 mutated subjects

Glucoregulation assessment DIAGNOSTIC_TEST

Fasted glycaemia and insulinaemia, glycated haemoglobin (HbA1c) and glycaemia following an oral glucose challenge test will be measured in all study subjects.

Healthy subjects; KCNQ1 mutated subjects

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the investigator's opinion, the subject is generally healthy based on their medical records (subjects with KCNQ1 mutation only), medical history, physical examination, vital signs, body weight, ECG (except long QT if applicable), and based on the results of haematology, clinical chemistry, urinalysis, urine drug screen (UDS) and serology;
• Subjects with a KCNQ1 mutation: genotyped as having a mutation on the KCNQ1 gene with or without phenotypic manifestation of long QT syndrome;
• Relatives of subjects with a KCNQ1 mutation: KCNQ1-mutated family relatives (with or without phenotypic expression) of a subject carrying a KCNQ1 mutation (Romano-Ward patients or subjects without phenotypic manifestation of long QT syndrome);
• Relatives of subjects with a KCNQ1 mutation must live in a different household than the subject with the KCNQ1 mutation;
• All subjects: negative UDS by dipstick analysis: opiates, methadone, cocaine, amphetamines (including ecstasy), barbiturates, benzodiazepines, and cannabinoids at admission to the assessment visit;
• All subjects: negative alcohol breath test at admission to the assessment visit.

You may not qualify if:

• All subjects: having taken within 1 year before the assessment visit or currently taking any of the following medications: a. Antidiabetics: metformin, pioglitazone, acarbose, miglitol, sitagliptin, vildagliptin, saxagliptin, exenatide, liraglutide, semaglutide, repaglinide, nateglinide, insulin. b. Medications interfering with the central nervous system (CNS) such as any antipsychotic, antidepressant or regular use of anxiolytic medications \> once a week, or any attention deficit/hyperactivity disorder (ADHD) medication (e.g. methylphenidate);
• Healthy subjects and relatives of subjects with a KCNQ1 mutation not phenotypically affected: any of the following on a de novo ECG: a. Heart rate (HR) \< 40 bpm or \> 100 bpm; b. PR interval \<120 msec; c. Abnormal repolarization; d. QT interval corrected for HR using Fridericia's formula (QTcF) \> 450 msec for male subjects or \> 470 msec for female subjects.

Sponsors & Collaborators

• Biotrial: lead
• European Union: collaborator
• Nantes University Hospital: collaborator

Study Sites (2)

L'Institut du Thorax, Nantes Hospital

Nantes, 44000, France

RECRUITING

Biotrial Clinical Unit

Rennes, 35000, France

NOT YET RECRUITING

Related Publications (9)

• Torekov SS, Iepsen E, Christiansen M, Linneberg A, Pedersen O, Holst JJ, Kanters JK, Hansen T. KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia. Diabetes. 2014 Apr;63(4):1315-25. doi: 10.2337/db13-1454. Epub 2013 Dec 18.

  PMID: 24357532 BACKGROUND

• van de Vondervoort I, Poelmans G, Aschrafi A, Pauls DL, Buitelaar JK, Glennon JC, Franke B. An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive-compulsive disorder. J Psychiatry Neurosci. 2016 Jun;41(4):280-5. doi: 10.1503/jpn.140327.

  PMID: 26854754 BACKGROUND

• van de Vondervoort IIGM, Amiri H, Bruchhage MMK, Oomen CA, Rustogi N, Cooper JD, van Asten JJA, Heerschap A, Bahn S, Williams SCR, Buitelaar JK, Poelmans G, Glennon JC. Converging evidence points towards a role of insulin signaling in regulating compulsive behavior. Transl Psychiatry. 2019 Sep 12;9(1):225. doi: 10.1038/s41398-019-0559-6.

  PMID: 31515486 BACKGROUND

• Southgate L, Tchanturia K, Collier D, Treasure J. The development of the childhood retrospective perfectionism questionnaire (CHIRP) in an eating disorder sample. Eur Eat Disord Rev. 2008 Nov;16(6):451-62. doi: 10.1002/erv.870.

  PMID: 18444228 BACKGROUND

• Foa EB, Huppert JD, Leiberg S, Langner R, Kichic R, Hajcak G, Salkovskis PM. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess. 2002 Dec;14(4):485-96.

  PMID: 12501574 BACKGROUND

• Lynam, D.R., Smith, G.T., Whiteside, S.P., Cyders, M.A. (2006). The UPPS-P: Assessing five personality pathways to impulsive behavior (Technical Report). West Lafayette: Purdue University.

  BACKGROUND

• Zermatten, A., Van der Linden, M., Jermann, F., Ceschi, G. Validation of a French version of the Obsessive-Compulsive Inventory-Revised in a non-clinical sample. (2006). Revue Européenne de Psychologie Appliquée. 56:151-155

  BACKGROUND

• Van der Linden, M., d'Acremont, M., Zermatten, A., Jermann, F., Laroi, F., Willems, S., Juillerat, A., Bechara, A. (2006). A French Adaptation of the UPPS Impulsive Behavior Scale: Confirmatory factor analysis in a sample of undergraduate students. Eur J Psychol Assess. 22:38-42.

  BACKGROUND

• Fatima SS, Chaudhry B, Khan TA, Farooq S. KCNQ1 rs2237895 polymorphism is associated with Gestational Diabetes in Pakistani Women. Pak J Med Sci. 2016 Nov-Dec;32(6):1380-1385. doi: 10.12669/pjms.326.11052.

  PMID: 28083030 RESULT

Related Links

• Official website of the PRIME project
• Biotrial's website

MeSH Terms

Conditions

Romano-Ward Syndrome; Long QT Syndrome; Compulsive Behavior

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Impulsive Behavior; Behavior

Study Officials

• Sophie Hays, MD

  Biotrial

  PRINCIPAL INVESTIGATOR

• Probst Vincent, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valerie Bertaina-Anglade, PhD

CONTACT

+33 (0)2 99 59 91 91; Valerie.Bertaina-Anglade@biotrial.com

Philippe Danjou, MD

CONTACT

+33 (0)9 75 51 88 82; Philippe.Danjou@biotrial.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2021
• First Posted: January 20, 2021
• Study Start: January 8, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: January 20, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Individual participant data will be available starting in january 2023 and until december 2025

Locations

FR (2)