The Day-time Response Variation of (Lis)Dexamphetamine
Condition: Adhd
Study type: Observational

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.
    

Intervention name(s): Dexamfetamine Sulfate 5 Mg Oral Tablet; Lisdexamfetamine Dimesylate; blood samples
Intervention type(s): Drug; Drug; Biological
Intervention description(s): The dosage is set based on the recommendation of the practitioner. Dexamphetamine is administered twice a day, with an interval of 4 hours.; The dosage is set based on the recommendation of the practitioner. Lisdexamphetamine is only administered once a day.; The blood samples will be taken at set times: 0, 2, 4, 6, 9 and 12 (hours)
Other intervention name(s): Tentin; Elvanse; vena puncture
Intervention MeSH terms: Lisdexamfetamine Dimesylate; Dextroamphetamine
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.
      
Biospecimen description: 
      A total of 12 blood samples (2 ml per sample) per subject will be taken.
    
Keywords: Dexamphetamine; lisdexamphetamine; ADHD; QbTest; Pharmacokinetics and dynamics