Clinical trial NCT04946461: The Day-time Response Variation of (Lis)Dexamphetamine
Official title: Objectifying the Day-time Response Variation of (Lis)Dexamphetamine in Adults With ADHD
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adhd
Keywords: Dexamphetamine
lisdexamphetamine
ADHD
QbTest
Pharmacokinetics and dynamics
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: ADHDcentraal
First posted: 2021-06-30
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients who are diagnosed with ADHD according to the DSM 5 criteria (NVvP,2015 ref) at ADHDcentraal and where treatment as usual (TAU) with dex or lisdex already commenced but where the optimal dosage and type of amphetamine has not been established.

Brief summary: In the Netherlands, two forms of amphetamines are available for the treatment of ADHD in adults; dexamfetamine (Tentin) and lisdexamfetamine (Elvanse) and both belong to regular and primary care pharmacotherapy. Both drugs contain exactly the same substance dexamfetamine and it would be expected that the effects on the symptoms of ADHD and the duration of action should be comparable. Previous studies and daily practice have reported different effects and duration of action of both, however. In this study the investigators want to investigate this difference by giving both drugs to the same patient, objectify the blood concentrations, objective and subjective effects and hope to be able to further optimize the treatment for ADHD with amphetamines.

Detailed description: Rationale: In the Netherlands, two types of amphetamines are available for the treatment of adults with ADHD: dexamphetamine sulfate (dex\[Tentin ©\]) and lisdexamphetamine dimesylate (lisdex \[Elvanse ©\]) Lisdex is promoted by the manufacturer as a long-acting preparation with a controlled release profile and thus an extended duration of action compared to dex, however, the scientific evidence about the pharmacokinetic (PK) / dynamic (PD) profile of lisdex compared to dex is sparse. Additionally, there are no head-to-head comparisons between dex and lisdex where an objective measurement for the symptom amelioration of ADHD has been used and compared to the plasma concentrations. The hypothesis is that two-times daily dex is more effective in suppressing ADHD symptomatology than once daily lisdex.

Objective: The objective is to compare the pharmacodynamic profile of dex and lisdex in adult patients with ADHD and determine whether the day-time response variation in ADHD symptomatology depends on the type of amphetamine and it's pharmacokinetics.

Study design: An observational study.

Study population: N=16 adults with a minimal age of 18 years old, diagnosed with ADHD according to the DSM 5 criteria, where treatment as usual (TAU) with dex or lisdex already commenced but where the optimal dosage and type of amphetamine have not been established.

Intervention: Sixteen participants will be observed for two consecutive days and PK/PD profiles of lisdex and dex will be observed. Lisdex will be bioequivalently dosed; lisdex once a day and dex two times a day with an interval of 4 hours (TAU). The participants will be observed for approximately 14 hours each day. Blood samples, the Quantified behavior Test (QbTest), physical measurements and questionnaires for drug effects will be taken 6 times at; 0, 2; 4; 6; 9; 12 (hours).

Main study parameters/endpoints: The primary study parameters are the PK/PD profile over time; next to blood samples for pharmacokinetic profiling pharmacodynamic assessments include the QbTest, the drug effect Questionnaire (DEQ), the Bond-Lader Visual Analog Scale (BL-VAS), QbTest performance questionnaire and physical measurements; blood pressure and heart rate.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no specific benefits for the study participants. The burden of participating in this study include two extra visits to the outpatient clinic. During each visit the study participant has to fill out some questionnaires, undergo six QbTests and bloodtests. In our opinion the burden for each study participant is considered minor and the risk very low. The therapy given during the study is according to the TAU, which is based on the guidelines of the Dutch association of psychiatry (NVvP) for the treatment of ADHD in adults. The participants will undergo a total of 12 blood samples (2ml per sample). This risk is acceptable in relation to the possible benefits that may be gained from this study, i.e. improved pharmacotherapy guidelines for adult patients with ADHD.

Eligibility criteria: Inclusion Criteria:

1. Participant is aged between 18 - 60 years at time of diagnosis
2. Participant is diagnosed with ADHD according to the DSM 5 criteria
3. Participant started pharmacotherapy treatment with dex or lisdex but no real preference for the type of amphetamine exists according to practitioner
4. Participant is able to provide written informed consent
5. Participant is able and willing to comply with the study protocol

Exclusion Criteria:

1. No diagnosis for ADHD
2. Currently other psychopharmacotherapy treatment than dex or lisdex
3. Currently other psychopharmacotherapy parallel to dex or lisdex

Primary outcomes:
measure: Quantified behavior Test (QbTest)
timeFrame: Two consecutive days; the QbTest assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Drug Effects Questionnaire (DEQ)
timeFrame: Two consecutive days; the DEQ assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Bond-Lader Visual Analog Scale (BL-VAS)
timeFrame: Two consecutive days; the BL-VAS assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: QbTest performance questionnaire
timeFrame: Two consecutive days; the QbTest performance questionnaire assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: systolic blood pressure (mmHg)
timeFrame: Two consecutive days; the cardiovasculaire assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Diastolic blood pressure (mmHg)
timeFrame: Two consecutive days; the cardiovasculaire assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Heart rate (heart beats per minute)
timeFrame: Two consecutive days; the cardiovasculaire assessments will be conducted at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Plasma concentration of D-amphetamine
timeFrame: Two consecutive days; the plasma concentration of D-amphetamine will be determined at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
Secondary outcomes:
measure: Compare area under the curve (AUC) of dex and lisdex
timeFrame: Two consecutive days; blood will be collected at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Compare maximum plasma concentration (Cmax) between lisdex and dex
timeFrame: Two consecutive days; blood will be collected at 6 time points during each day. At baseline (0), repeated after 2, 4, 6, 9 and 12 (hours)
measure: Compare time to reach maximum plasma concentration (Tmax) between lisdex and dex
timeFrame: Two consecutive days; blood will be collected at time points: 0, 2, 4, 6, 9 and 12 (hours)
Other outcomes:
measure: The Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Two consecutive days; the LSEQ will only be conducted at baseline (T0) for each study day
Locations:
city: Amsterdam
country: Netherlands
facility: ADHDcentraal
state: Noord Holland
Study officials:
affiliation: AUMC, location AMC
name: R. Mathot, PhD
role: PRINCIPAL_INVESTIGATOR
References: