Attention Deficit Disorder with HyperactivityPhase 2LAMAinDiabNCT05957055
Lisdexamphetamine Vs Methylphenidate for Pediatric Patients with ADHD and Type 1 Diabetes
A Phase 2 study testing parental training in behavior management, Lisdexamfetamine and Methylphenidate in people with Attention Deficit Disorder with Hyperactivity and Diabetes Mellitus, Type 1, run by Medical University of Lodz at 1 site in Poland.
Trial 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). Read more about this study
- Who is it for?
- Ages 8 years to 198 months
- Conditions the study is for
- Attention Deficit Disorder with Hyperactivity, Diabetes Mellitus, Type 1
- What is being tested?
- parental training in behavior management, Lisdexamfetamine and Methylphenidate
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 sitePoland
- Study dates
- 5 Feb 2024to 1 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years to 198 months
- All sexes
- No healthy volunteers
- Child
Principal inclusion criteria:
- 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
Principal exclusion criteria:
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
Pediatric Center of the Central Clinical Hospital of the Medical University of Lodz
Lodz, Łódź Voivodeship, 91-738
About this study
Official title: LAMAinDiab - Lisdexamphetamine Vs Methylphenidate for Pediatric Patients with ADHD and Type 1 Diabetes - a Randomized Cross-over Clinical Trial
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.
Read the detailed description
This is a multicenter, randomized, open-label, cross-over 2nd phase clinical trial in children and adolescents with attention deficit disorder with hyperactivity (ADHD) and type 1 diabetes mellitus (T1D), conducted in four Polish reference pediatric diabetes centers that together provide care for around 25% of Polish pediatric population with T1D.
T1D is a chronic pediatric disorder that requires intensive treatment with subcutaneous insulin, constant monitoring and frequent decision-making from the patient. Its course may be further complicated by comorbidities such as ADHD, which is present in around 5% of general population and reportedly more common in those with T1D. Despite the recognized need for psychiatric screening in children with T1D, ADHD often remains undiagnosed and untreated, resulting in worse therapy adherence and glycemic control, as well increased risk of life-threatening acute diabetes complications.
Each patient will begin the trial starting with the enrollment appointment, followed by a baseline assessment by a diabetologist and a psychological evaluation. After 2-weeks preliminary observation period, the parents/legal guardians of the patient will start a cycle of 10 meetings (one every week, 90 minutes long). Patients will be enrolled in an online once-weekly parental training in behavior management (PT) for ten weeks. The PT will be carried out in small groups (4-6 families per session) and conducted by a qualified and experienced PT therapist and supplemented with homework and educational materials. Qualification for pharmacological treatment will be carried out for those patients who complete the entire PT cycle, defined as the presence of at least 8 out of 10 meetings confirmed by the trainer. This is the designated expert threshold at which an intervention can be considered as carried out correctly. If the parents/legal guardians do not hold the required number of meetings, they will be allowed to make up for the missing classes during the next series of meetings with another group. If the parents/legal guardians do not attend the missing activities during this trial, the child will be excluded from the study.
After completion of PT, each participant will repeat the psychological evaluation to assess the effects of PT intervention alone on ADHD symptoms severity. Those with sustained clinically-significant ADHD symptoms will be qualified for pharmacological intervention. The patient's will be evaluated on diabetologists visit for contraindications to pharmacotherapy, including urine tests (pregnancy and panel test for substance use), ECG with QT segment assessment (to exclude long QT syndrome) and ophthalmological consultation (to exclude glaucoma). Subsequent and final assessment and qualification will be performed by psychiatrist during the nearest online consultation, after which patients will be randomized to pharmacotherapy groups: methylphenidate (MPH, long-release capsule, standard of care) versus lisdexamfetamine (LDX, investigated treatment).
Dose escalation for each drug will be performed over three (up to four) psychiatric consultations during the initial 5-7 weeks. LDX will be started with 30mg once-daily, administered orally, with dose change increment of 20mg every (after 1st, 3rd, 5th and 7th week, to the maximum of 70mg). MPH will be started with 18mg once-daily, administered orally, with dose change incremental of 18mg (after 1st, 3rd, 5th and 7th week, to the maximum of 54mg).
After the maximum tolerated dose is established, patients will continue pharmacotherapy for 6 months. During that time, treatment safety and efficacy will be evaluated twice - after first 3 months by psychological and diabetes care team's evaluation (with small dose adjustments allowed) and after full course (6 months) of therapy. On-demand psychiatric consultations will be allowed. In addition, during both diabetologists visits each participant will donate a dry blood sample for evaluation of the concentration of an allocated drug, and another sample will be self-collected on the day of the final psychological assessment for that arm to ensure that endpoint measurements are not biased by incidental non-adherence. After the last evaluation, participants will return the unused drug to their diabetes care center and will begin a wash-out period. and the treatment will continue for 6 months.
Qualification for the second arm of pharmacotherapy will be based on the same procedures and consultations which will be performed in parallel with the last diabetologists assessment (this means the participant will be on the drug at that time). Final switch and start of the second drug (LDX or MPH) will be based on psychiatrist decision. Its dose adjustment, safety and efficacy monitoring will follow the same procedures over the next 6 months.
The trial primary endpoint (ADHD symptom severity) will be assessed using the Conners 3.0 questionnaire by an investigator blinded to current treatment. Secondary endpoints will include metabolic control assessed with HbA1c and continuous glucose monitoring, and Quality of Life (QoL, measured by PedsQL). Exploratory endpoints will include school attendance, physical activity and sleep parameters (measured with personal wrist activity monitor), change in ADHD symptoms and diabetes control after PT alone, and change in rate of diabetes complications (severe hypoglycemia and diabetic ketoacidosis - rate and associated length of required inpatient treatment).
The primary goal of the trial is to improve ADHD treatment in children with T1D, and assess if treatment efficacy with lisdexamfetamine compared to methylphenidate may lead to both the psychiatric and metabolic benefits. The trial will provide patients with coordinated T1D and ADHD care, access to ADHD medication and PT (MPH is only partially reimbursed in Poland, LDX is unavailable on the Polish market, and PT is not reimbursed in the standard care).
- Being tested
- parental training in behavior management, Lisdexamfetamine, Methylphenidate
- Keywords
- attention deficit disorder with hyperactivity, diabetes mellitus, type 1, methylphenidate, lisdexamfetamine dimesylate, adolescent, child, glycemic variability, randomized cross-over trial, continuous glucose monitoring
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
parental training in behavior managementBehavioural
Also called PT training
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.
LisdexamfetamineDrug
Also called LDX
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).
MethylphenidateDrug
Also called MPH
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: parental training in behavior management; Drug: Lisdexamfetamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in glycated haemoglobin (HbA1c).
Measured: 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
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: percentage of time patient's sensor glucose values were in the target range (70-180mg/dl).
Measured: 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)
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: percentage of time patient's sensor glucose values were in the hypoglycemia range (<70mg/dl).
Measured: 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)
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: percentage of time patient's sensor glucose values were in the clinically significant hypoglycemia range (<54mg/dl).
Measured: 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)
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: percentage of time patient's sensor glucose values were in the hyperglycemia range (>180mg/dl).
Measured: 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 >250mg/dL (significant hyperglycemia)
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: percentage of time patient's sensor glucose values were in the significant hyperglycemia (>250mg/dl) range.
Measured: 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 mean sensor glucose
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: mean sensor glucose
Measured: 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 coefficient of variation
Change of metabolic control of Type 1 Diabetes Mellitus, quantified as the difference in the continuous glucose monitoring derived parameters: coefficient of variation (calculated as the ratio of the standard deviation to mean sensor glucose, expressed as a percentage).
Measured: 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)
Improvement of the patient's quality of life (QoL)
The outcome will be measured using PedsQL 3.2 questionnaires, completed by patient and parent/legal guardian, assessed by an investigator blinded to patient allocation.
Measured: Improvement of the patient's quality of life (QoL) measured from baseline (within 2 weeks before PT training), after completion of PT training (week 10th/22nd) and after each 6 months of pharmacotherapy arm
Number of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "inattention" scale
Number of trial participants achieving an improvement in ADHD symptom severity of at least 1/3 of the baseline value at the end of a given pharmacological intervention, assessed separately on the basis of Conners 3 "inattention" scale. Endpoint assessment by an investigator blinded to patient allocation.
Measured: Measured 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
Percentage of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "inattention" scale
Percentage of trial participants achieving an improvement in ADHD symptom severity of at least 1/3 of the baseline value at the end of a given pharmacological intervention, assessed separately on the basis of Conners 3 "inattention" scale. Endpoint assessment by an investigator blinded to patient allocation.
Measured: Measured 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
Number of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "hyperactivity/impulsivity" scale
Number of trial participants achieving an improvement in ADHD symptom severity of at least 1/3 of the baseline value at the end of a given pharmacological intervention, assessed separately on the basis of Conners 3 "hyperactivity/impulsivity" scale. Endpoint assessment by an investigator blinded to patient allocation.
Measured: Measured 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
Percentage of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "hyperactivity/impulsivity" scale
Percentage of trial participants achieving an improvement in ADHD symptom severity of at least 1/3 of the baseline value at the end of a given pharmacological intervention, assessed separately on the basis of Conners 3 "hyperactivity/impulsivity" scale. Endpoint assessment by an investigator blinded to patient allocation.
Measured: Measured 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2023
- Study start5 Feb 2024
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Disorder with HyperactivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Interventional, open, randomized (block randomization stratified by center), assessor masked, cross-over
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Lodz
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of Silesia, Medical University of Gdansk, Institute of Medical Sciences of the University of Opole, Pediatric Center of the Central Clinical Hospital of the Medical University of Lodz
- Responsible party
- Sponsor
- Investigators
- Agnieszka Butwicka, A/Prof, Principal investigator, Department of Biostatistics and Translational Medicine, Medical University of Lodz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05957055
- Sponsor's protocol ID
- LAMA/2021/1
- Other IDs
- 2022-001906-24, 2021/ABM/02/00006/P/03, UR/DBL/D/263/2022
- Acronym
- LAMAinDiab
- Status last verified
- Nov 2024
- First submitted
- 30 Jun 2023
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data (with Protected Health Information included) will be provided only in case of serious adverse events and suspected unexpected serious adverse reactions and only to applicable regulators and monitor institutions under appropriate regulations and applicable law.
Publications
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.
PubMed 38086595
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LAMAinDiab - Lisdexamphetamine Vs Methylphenidate for Pediatric Patients with ADHD and Type 1 Diabetes - a Randomized Cross-over Clinical Trial
- ClinicalTrials.gov ID
- NCT05957055
- Acronym / sponsor ID
- LAMAinDiab / LAMA/2021/1
- Keywords
- attention deficit disorder with hyperactivity, diabetes mellitus, type 1, methylphenidate, lisdexamfetamine dimesylate, adolescent, child, glycemic variability, randomized cross-over trial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Medical University of LodzUniversity, hospital or other
- Collaborators
- Medical University of Silesia, Medical University of Gdansk, Institute of Medical Sciences of the University of Opole, Pediatric Center of the Central Clinical Hospital of the Medical University of Lodz
- Study start
- 5 Feb 2024 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 24 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, randomized, open-label, cross-over 2nd phase clinical trial in children and adolescents with attention deficit disorder with hyperactivity (ADHD) and type 1 diabetes mellitus (T1D), conducted in four Polish reference pediatric diabetes centers that together provide care for around 25% of Polish pediatric population with T1D.
T1D is a chronic pediatric disorder that requires intensive treatment with subcutaneous insulin, constant monitoring and frequent decision-making from the patient. Its course may be further complicated by comorbidities such as ADHD, which is present in around 5% of general population and reportedly more common in those with T1D. Despite the recognized need for psychiatric screening in children with T1D, ADHD often remains undiagnosed and untreated, resulting in worse therapy adherence and glycemic control, as well increased risk of life-threatening acute diabetes complications.
Each patient will begin the trial starting with the enrollment appointment, followed by a baseline assessment by a diabetologist and a psychological evaluation. After 2-weeks preliminary observation period, the parents/legal guardians of the patient will start a cycle of 10 meetings (one every week, 90 minutes long). Patients will be enrolled in an online once-weekly parental training in behavior management (PT) for ten weeks. The PT will be carried out in small groups (4-6 families per session) and conducted by a qualified and experienced PT therapist and supplemented with homework and educational materials. Qualification for pharmacological treatment will be carried out for those patients who complete the entire PT cycle, defined as the presence of at least 8 out of 10 meetings confirmed by the trainer. This is the designated expert threshold at which an intervention can be considered as carried out correctly. If the parents/legal guardians do not hold the required number of meetings, they will be allowed to make up for the missing classes during the next series of meetings with another group. If the parents/legal guardians do not attend the missing activities during this trial, the child will be excluded from the study.
After completion of PT, each participant will repeat the psychological evaluation to assess the effects of PT intervention alone on ADHD symptoms severity. Those with sustained clinically-significant ADHD symptoms will be qualified for pharmacological intervention. The patient's will be evaluated on diabetologists visit for contraindications to pharmacotherapy, including urine tests (pregnancy and panel test for substance use), ECG with QT segment assessment (to exclude long QT syndrome) and ophthalmological consultation (to exclude glaucoma). Subsequent and final assessment and qualification will be performed by psychiatrist during the nearest online consultation, after which patients will be randomized to pharmacotherapy groups: methylphenidate (MPH, long-release capsule, standard of care) versus lisdexamfetamine (LDX, investigated treatment).
Dose escalation for each drug will be performed over three (up to four) psychiatric consultations during the initial 5-7 weeks. LDX will be started with 30mg once-daily, administered orally, with dose change increment of 20mg every (after 1st, 3rd, 5th and 7th week, to the maximum of 70mg). MPH will be started with 18mg once-daily, administered orally, with dose change incremental of 18mg (after 1st, 3rd, 5th and 7th week, to the maximum of 54mg).
After the maximum tolerated dose is established, patients will continue pharmacotherapy for 6 months. During that time, treatment safety and efficacy will be evaluated twice - after first 3 months by psychological and diabetes care team's evaluation (with small dose adjustments allowed) and after full course (6 months) of therapy. On-demand psychiatric consultations will be allowed. In addition, during both diabetologists visits each participant will donate a dry blood sample for evaluation of the concentration of an allocated drug, and another sample will be self-collected on the day of the final psychological assessment for that arm to ensure that endpoint measurements are not biased by incidental non-adherence. After the last evaluation, participants will return the unused drug to their diabetes care center and will begin a wash-out period. and the treatment will continue for 6 months.
Qualification for the second arm of pharmacotherapy will be based on the same procedures and consultations which will be performed in parallel with the last diabetologists assessment (this means the participant will be on the drug at that time). Final switch and start of the second drug (LDX or MPH) will be based on psychiatrist decision. Its dose adjustment, safety and efficacy monitoring will follow the same procedures over the next 6 months.
The trial primary endpoint (ADHD symptom severity) will be assessed using the Conners 3.0 questionnaire by an investigator blinded to current treatment. Secondary endpoints will include metabolic control assessed with HbA1c and continuous glucose monitoring, and Quality of Life (QoL, measured by PedsQL). Exploratory endpoints will include school attendance, physical activity and sleep parameters (measured with personal wrist activity monitor), change in ADHD symptoms and diabetes control after PT alone, and change in rate of diabetes complications (severe hypoglycemia and diabetic ketoacidosis - rate and associated length of required inpatient treatment).
The primary goal of the trial is to improve ADHD treatment in children with T1D, and assess if treatment efficacy with lisdexamfetamine compared to methylphenidate may lead to both the psychiatric and metabolic benefits. The trial will provide patients with coordinated T1D and ADHD care, access to ADHD medication and PT (MPH is only partially reimbursed in Poland, LDX is unavailable on the Polish market, and PT is not reimbursed in the standard care).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Interventional, open, randomized (block randomization stratified by center), assessor masked, cross-over
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate first, lisdexamfetamine second | Active comparator | Behavioral: parental training in behavior management, Drug: MethylphenidateInitial 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. |
| Lisdexamfetamine first, methylphenidate second | Active comparator | Behavioral: parental training in behavior management, Drug: LisdexamfetamineInitial 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. |
Who may qualify
- Ages
- 8 years to 198 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| parental training in behavior managementAlso: PT trainingParental 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. | Behavioural | Lisdexamfetamine first, methylphenidate second, Methylphenidate first, lisdexamfetamine second |
| LisdexamfetamineAlso: LDXOnce-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). | Drug | Lisdexamfetamine first, methylphenidate second |
| MethylphenidateAlso: MPHOnce-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). | Drug | Methylphenidate first, lisdexamfetamine second |
Primary outcome
Change in ADHD symptom scores on the "inattention" scale of the Conners 3 questionnaire
Time frame: 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 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.
Change in ADHD symptom scores on the "hyperactivity/impulsivity" scale of the Conners 3 questionnaire
Time frame: 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 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.
The number of adverse events - methylphenidate arm
Time frame: Events recorded throughout treatment with MPH for 6 months after randomization or cross-over
The number of adverse events coded following the MedDRA dictionary.
The frequency of adverse events - methylphenidate arm
Time frame: Events recorded throughout treatment with MPH for 6 months after randomization or cross-over.
The frequency of adverse events per patient-month coded following the MedDRA dictionary.
The number of adverse events - lisdexamphetamine arm
Time frame: Events recorded throughout treatment with LDX for 6 months after randomization or cross-over
The number of adverse events coded following the MedDRA dictionary.
The frequency of adverse events - lisdexamphetamine arm
Time frame: Events recorded throughout treatment with LDX for 6 months after randomization or cross-over
The frequency of adverse events per patient-month coded following the MedDRA dictionary.
13 secondary outcomes
Change in Type 1 Diabetes Mellitus metabolic control - glycated haemoglobin
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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 >250mg/dL (significant hyperglycemia)
Time frame: 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 mean sensor glucose
Time frame: 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 coefficient of variation
Time frame: 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)
Improvement of the patient's quality of life (QoL)
Time frame: Improvement of the patient's quality of life (QoL) measured from baseline (within 2 weeks before PT training), after completion of PT training (week 10th/22nd) and after each 6 months of pharmacotherapy arm
Number of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "inattention" scale
Time frame: Measured 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
Percentage of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "inattention" scale
Time frame: Measured 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
Number of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "hyperactivity/impulsivity" scale
Time frame: Measured 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
Percentage of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "hyperactivity/impulsivity" scale
Time frame: Measured 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Background: PubMed 38086595Michalak 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.
- Individual participant dataSharing planned: No. Individual Participant Data (with Protected Health Information included) will be provided only in case of serious adverse events and suspected unexpected serious adverse reactions and only to applicable regulators and monitor institutions under appropriate regulations and applicable law.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Agnieszka Butwicka, A/Prof principal investigator
Department of Biostatistics and Translational Medicine, Medical University of Lodz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing parental training in behavior management, Lisdexamfetamine and Methylphenidate in people with Attention Deficit Disorder with Hyperactivity and Diabetes Mellitus, Type 1, run by Medical University of Lodz at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agnieszka Butwicka, A/Prof (+46 72 326 66 31, agnieszka.butwicka@umed.lodz.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ADHD symptom scores on the "inattention" scale of the Conners 3 questionnaire (time frame: 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 study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05957055, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.