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.

The Day-time Response Variation of (Lis)Dexamphetamine

Adhd

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.

Dexamfetamine Sulfate 5 Mg Oral Tablet

Lisdexamfetamine Dimesylate

blood samples

Objectifying the Day-time Response Variation of (Lis)Dexamphetamine in Adults With ADHD

The pharmacodynamic profile (PD) will be compared to the pharmacokinetic profile to objectify the day-time response variation for both types of amphetamines.
The QbTest will be used as a PD measure. The QbTest was the world's first FDA cleared, and CE marked ADHD management system. QbTest is a test which objectively evaluates the core symptoms of ADHD for children and adults by combining motion-tracking analysis with a uniquely designed continuous performance task. The test results are compared with an age, length, weight and gender adjusted norm group to set the context to the patient's performance and corresponds to Z-scores (norm population M = 0 and SD =1, SD > 1.5 should be viewed as atypical and give cause for clinical concern).

The pharmacodynamic profile (PD) will be compared to the pharmacokinetic profile to objectify the day-time response variation for both types of amphetamines. The DEQ will be used as a PD measure.
The DEQ is a concise questionnaire, its questions have been widely used and it has shown promising results regarding its psychometric properties. DEQ is therefore suitable for the current study.
The DEQ consists of 5 items (VAS) that represent the following dimensions: feel of any substance effects (FEEL), feeling of being high (HIGH), drug-liking (LIKE), drug-disliking (DISLIKE) and drug-wanting (MORE). The answers are obtained using a digital VAS scale with numbers that show the values 1 - 100. E.g., A higher score on the LIKE scale represents a higher amount of drug-liking.

The pharmacodynamic profile (PD) will be compared to the pharmacokinetic profile to objectify the day-time response variation for both types of amphetamines. The BL-VAS will be used as a PD measure.
The Bond & Lader VAS Mood Rating Scale (BL-VAS) is used to measure the effects of drugs on the participants' mood. The BL-VAS consists of 16 items. The responses are obtained using digital VAS that show the values 1 - 100. The reponses are combined into three dimensions that represent mood, namely: alertness (n = 9), calmness (n = 2) and contentedness (n = 5). The scores of the individual items are summed and averaged, this results in a score for each factor. The range of the factor is 1 - 100. A higher score represents a higher degree of alertness, calmness or contentedness

The pharmacodynamic profile (PD) will be compared to the pharmacokinetic profile to objectify the day-time response variation for both types of amphetamines. The QbTest performance questionnaire will be used as a PD measure.
Participants will perform the QbTest six times a day, immediately after the collection of blood samples. After the QbTest, participants will be shortly questioned about their perception regarding the performance, focus and energy during the test. The questionnaire consists of 4 questions regarding hyperfocus, energy and performance. The responses are obtained using digital VAS that show the values 1 - 100. The scores of the individual items are summed and averaged, this results in a score for each factor. The range of the factor is 1 - 100. A higher score represents a higher degree of performance.

The pharmacodynamic profile (PD) will be compared to the pharmacokinetic profile to objectify the day-time response variation for both types of amphetamines. The Cardiovasculaire response will be used as a PD measure.
Cardiovascular response included blood pressure (diastolic and systolic) and hart rate (puls).

The pharmacodynamic profile (PD) will be compared to the pharmacokinetic profile to objectify the day-time response variation for both types of amphetamines. The Cardiovasculaire response will be used as a PD measure.
Cardiovascular response included blood pressure (diastolic and systolic) and heart rate (puls).

The PD profiles will be compared to the PK profiles to objectify the day-time response variation for both types of amphetamines. Blood samples, 2ml each, will be collected in lithium heparin tubes 0, 2, 4, 6, 9, 12 h after drug administration. Thereby, the plasma concentration of D-amphetamine can be determined.

Principal investigator

Compare the AUC of dex and lisdex, the investigators hypothesize that the AUC between dex and lisdex will be identical, and the current conversion factor for bioequivalence between dex and lisdex is appropriate.

The investigators hypothesize that the Cmax for lisdex will be higher compared to dex.

The investigators hypothesize that Lisdex will have higher drug-liking scores at Tmax than dex.
The investigators hypothesize that Lisdex will have more side-effects at Tmax than dex.

subjects are assigned to group 1 based on the type of medication prescribed by the practitioner. Subjects which started with lisdexamphetamine are assigned to group 1.

subjects are assigned to group 2 based on the type of medication prescribed by the practitioner. Subjects which started with dexamphetamine are assigned to group 1.

The Day-time Response Variation of (Lis)Dexamphetamine

About this trial

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Placebo

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