Lisdexamphetamine Vs Methylphenidate for Pediatric Patients with ADHD and Type 1 Diabetes

NCT05957055 | Recruiting Phase 2 DMC

• 4 other identifiers: LAMA/2021/12022-001906-242021/ABM/02/00006/P/03UR/DBL/D/263/2022
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to evaluate the safety and effectiveness of an intervention involving parental training in behaviour management and medication in children with both Type 1 Diabetes (T1D) and Attention Deficit Disorder with Hyperactivity (ADHD). ADHD is a neurodevelopmental disorder that affects around 5% of school-age children and adolescents, while T1D is a chronic disease requiring strict management. After initial parental training provided for parents/legal guardians, the children will be randomized to one of two cross-over groups, and treated with either lisdexamfetamine or methylphenidate first. After dose optimization for first 5-7 weeks, patients will be treated for 6 months total, after which they will be switched to the other drug. Researchers will then compare the ADHD symptom severity as measured by Conners 3 questionnaire, and compare the frequency of any adverse events associated with the therapy. As secondary outcomes, patient's T1D control and quality of life will be compared between the two drugs.

Conditions

Attention Deficit Disorder with Hyperactivity; Diabetes Mellitus, Type 1

Keywords

attention deficit disorder with hyperactivity; diabetes mellitus, type 1; methylphenidate; lisdexamfetamine dimesylate; adolescent; child; glycemic variability; randomized cross-over trial; continuous glucose monitoring

Outcome Measures

Primary Outcomes (6)

• Change in ADHD symptom scores on the "inattention" scale of the Conners 3 questionnaire

  Change of ADHD symptom severity, measured as the difference in ADHD symptom score on the "inattention" scale of the Conners 3 questionnaire (completed by patient and parent/legal guardian), assessed by the investigator blinded to patient allocation.

  Before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug

• Change in ADHD symptom scores on the "hyperactivity/impulsivity" scale of the Conners 3 questionnaire

  Change of ADHD symptom severity, measured as the difference in ADHD symptom score on the "hyperactivity/impulsivity" scale of the Conners 3 questionnaire (completed by patient and parent/legal guardian), assessed by the investigator blinded to patient allocation.

  Before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug

• The number of adverse events - methylphenidate arm

  The number of adverse events coded following the MedDRA dictionary.

  Events recorded throughout treatment with MPH for 6 months after randomization or cross-over

• The frequency of adverse events - methylphenidate arm

  The frequency of adverse events per patient-month coded following the MedDRA dictionary.

  Events recorded throughout treatment with MPH for 6 months after randomization or cross-over.

• The number of adverse events - lisdexamphetamine arm

  The number of adverse events coded following the MedDRA dictionary.

  Events recorded throughout treatment with LDX for 6 months after randomization or cross-over

• The frequency of adverse events - lisdexamphetamine arm

  The frequency of adverse events per patient-month coded following the MedDRA dictionary.

  Events recorded throughout treatment with LDX for 6 months after randomization or cross-over

Secondary Outcomes (13)

• Change in Type 1 Diabetes Mellitus metabolic control - glycated haemoglobin

  Measured after 6 months of MPH or LDX treatment and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration)

• Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time in target range 70-180mg/dL

  Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days)

• Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time below target range <70mg/dL (hypoglycemia)

  MMeasured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days)

• Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time below target range <54mg/dL (clinically significant hypoglycemia)

  Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days)

• Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time above target range >180mg/dL (hyperglycemia)

  Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days)

Study Arms (2)

Methylphenidate first, lisdexamfetamine second

ACTIVE COMPARATOR

Initial treatment after PT training - methylphenidate (prolonged-release tablet) once-daily with dose optimization for 5-7 weeks and 6 months total therapy then change to lisdexamfetamine once-daily with dose optimization for 5-7 weeks and 6 months total therapy.

Behavioral: parental training in behavior management; Drug: Methylphenidate

Lisdexamfetamine first, methylphenidate second

ACTIVE COMPARATOR

Initial treatment after PT training - lisdexamfetamine once-daily with dose optimization for 5-7 weeks and 6 months total therapy then change to methylphenidate (prolonged-release tablet) once-daily with dose optimization for 5-7 weeks and 6 months total therapy.

Behavioral: parental training in behavior management; Drug: Lisdexamfetamine

Interventions

parental training in behavior management BEHAVIORAL

Parental training in behavior management - online group sessions (4-6 families within group) with trained specialist, 10 once-weekly sessions. To continue to pharmacotherapy, the parents/legal guardians are required to participate in at least 8 out of 10 sessions.

Also known as: PT training

Lisdexamfetamine first, methylphenidate second; Methylphenidate first, lisdexamfetamine second

Lisdexamfetamine DRUG

Once-daily pharmacotherapy with lisdexamfetamine (608137-32-2, SUB32146), administered orally, for a duration of 6 months with initial dose of 30mg and dose optimization for 5-7 weeks (visits after 1st, 3rd and 5th week of therapy to adjust dose, in 20mg steps).

Also known as: LDX

Lisdexamfetamine first, methylphenidate second

Methylphenidate DRUG

Once-daily pharmacotherapy with methylphenidate (prolonged-release tablet, 298-59-9, SUB03254MIG), administered orally, for a duration of 6 months with initial of 18mg dose optimization for 5-7 weeks (visits after 1st, 3rd and 5th week of therapy to adjust dose, in 18mg steps).

Also known as: MPH

Methylphenidate first, lisdexamfetamine second

Eligibility Criteria

• Age: 8 Years - 198 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 8-16.5 years at study entry;
• T1D diagnosed on the basis of clinical features, presence of autoantibodies typical for type 1 diabetes (at least one of the following: anti-glutamate decarboxylase, islet cell antibody, insulin autoantibody/islet antigen 2 autoantibody, zinc transporter 8 antibody) and/or low C-peptide levels (according to the laboratory standard appropriate for the assay method) and criteria for the diagnosis of diabetes according to the criteria of the Polish Diabetes Association and international societies:
• an incidental glycemia ≥200mg/dl and symptoms of hyperglycemia (such as increased thirst, polyuria, weakness) or
• two times a fasting blood glucose ≥125mg/dl or
• a blood glucose ≥200mg/dL in the 120th minute of an oral glucose load test or
• HbA1c ≥6.5%.
• T1D diagnosed at least 12 months before recruitment;
• T1D treated with functional intensive insulin therapy
• a diagnosis of ADHD according to Diagnostic and Statistical Manual 5 (DSM-5) criteria confirmed by a psychiatrist or a diagnosis of ADHD according to other criteria recognized in Poland, confirmed by an authorized person as consistent with DSM-5
• Polish citizenship and Polish health insurance

You may not qualify if:

• Daily insulin dose\<0.3 j/kg and concomitant HbA1c measurement ≤6.5% from the last 3 months (clinical partial remission of T1D);
• Severely unsatisfactory glycemic control - mean HbA1c over the past year ≥12% (not including HbA1c measurement at diagnosis of T1D);
• Diagnosed intellectual or other disability that prevents participation in the trial or adherence to its therapeutic regimen;
• Clinically apparent cardiovascular disease: recognized hemodynamically significant heart defect, advanced vascular atherosclerosis;
• Diagnosis of other mental illness or disorder preventing participation in the trial, e.g. bipolar affective disorder, schizophrenia, other psychotic disorders, psychoactive substance abuse;
• Diagnosed allergy or hypersensitivity to drugs used in pharmacological intervention -methylphenidate and/or lisdexamphetamine;
• Language barrier making it impossible to conduct a full psychological consultation in Polish;
• Lack of permanent residence in Poland;
• Contraindications as reported for investigated drugs: documented hypertension (at least stage 2), positive family history for sudden cardiac deaths and atrial arrythmias in relatives below 40 y.o., clinically evident glaucoma or abnormally elevated intraocular pressure, history of suicide attempts or present suicide intentions, oppositional defiant disorder, chronic motor tics or Tourette syndrome, pregnancy or breastfeeding, short stature, underweight (≤ 3rd percentile for reference percentile charts), epilepsy, pheochromocytoma, substance abuse or positive drug test results, prolonged treatment with sedative drugs (e.g., 1st generation antihistamines);
• Declared by the parents/legal guardians' inability or unwillingness to come to the Center at the time specified by the protocol, in particular - to pick up the Trial drugs at the dose adjustment stage (the need to pick up 4-5 times over 6-8 weeks, each time within 2-3 days of receiving the recommendations);
• Other reasons that, in the opinion of the attending physician, are more likely to result in difficulties in maintaining the continuity of the participant's participation in the trial or harm to the participant's health in case of participation in the trial.

Sponsors & Collaborators

• Medical University of Lodz: lead
• Medical University of Silesia: collaborator
• Medical University of Gdansk: collaborator
• Institute of Medical Sciences of the University of Opole: collaborator
• Pediatric Center of the Central Clinical Hospital of the Medical University of Lodz: collaborator

Study Sites (1)

Pediatric Center of the Central Clinical Hospital of the Medical University of Lodz

Lodz, Łódź Voivodeship, 91-738, Poland

RECRUITING

Related Publications (1)

• Michalak A, Chrzanowski J, Kusmierczyk-Koziel H, Klejman E, Blaziak K, Mianowska B, Szadkowska A, Chobot AP, Jarosz-Chobot P, Mysliwiec M, Makowska I, Kalenik A, Zamarlik M, Wolanczyk T, Fendler W, Butwicka A. Lisdexamphetamine versus methylphenidate for paediatric patients with attention-deficit hyperactivity disorder and type 1 diabetes (LAMAinDiab): protocol for a multicentre, randomised cross-over clinical trial in an outpatient telemedicine-supported setting. BMJ Open. 2023 Dec 12;13(12):e078112. doi: 10.1136/bmjopen-2023-078112.

  PMID: 38086595 BACKGROUND

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Diabetes Mellitus, Type 1

Interventions

Lisdexamfetamine Dimesylate; Methylphenidate; 5,10-dihydro-5-methylphenazine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Agnieszka Butwicka, A/Prof

  Department of Biostatistics and Translational Medicine, Medical University of Lodz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agnieszka Butwicka, A/Prof

CONTACT

+46 72 326 66 31; agnieszka.butwicka@umed.lodz.pl

Arkadiusz Michalak, MD

CONTACT

+48504867777; arkadiusz.michalak@umed.lodz.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: ADHD symptoms assessment will be performed with teleconsultation with outcomes assessor blinded for patient's allocation. Patients and their parents/legal guardians will be asked to not share the information with the assessor.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional, open, randomized (block randomization stratified by center), assessor masked, cross-over

Study Record Dates

• First Submitted: June 30, 2023
• First Posted: July 24, 2023
• Study Start: February 5, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)