Objectifying the Day-time Response Variation of (Lis)Dexamphetamine in Adults With ADHD
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Quantified behavior Test (QbTest)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is aged between 18 - 60 years at time of diagnosis
- •Participant is diagnosed with ADHD according to the DSM 5 criteria
- •Participant started pharmacotherapy treatment with dex or lisdex but no real preference for the type of amphetamine exists according to practitioner
- •Participant is able to provide written informed consent
- •Participant is able and willing to comply with the study protocol
排除标准
- •No diagnosis for ADHD
- •Currently other psychopharmacotherapy treatment than dex or lisdex
- •Currently other psychopharmacotherapy parallel to dex or lisdex
研究组 & 干预措施
group 1; lisdex - 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.
干预措施: Dexamfetamine Sulfate 5 Mg Oral Tablet (Drug)
group 1; lisdex - 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.
干预措施: Lisdexamfetamine Dimesylate (Drug)
group 1; lisdex - 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.
干预措施: blood samples (Biological)
group 2; dex - lisdex
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.
干预措施: Dexamfetamine Sulfate 5 Mg Oral Tablet (Drug)
group 2; dex - lisdex
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.
干预措施: Lisdexamfetamine Dimesylate (Drug)
group 2; dex - lisdex
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.
干预措施: blood samples (Biological)
结局指标
主要结局
Quantified behavior Test (QbTest)
时间窗: 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)
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).
Heart rate (heart beats per minute)
时间窗: 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)
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).
Drug Effects Questionnaire (DEQ)
时间窗: 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)
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.
Diastolic blood pressure (mmHg)
时间窗: 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)
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).
Plasma concentration of D-amphetamine
时间窗: 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)
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.
Bond-Lader Visual Analog Scale (BL-VAS)
时间窗: 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)
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
systolic blood pressure (mmHg)
时间窗: 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)
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).
QbTest performance questionnaire
时间窗: 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)
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.
次要结局
- Compare area under the curve (AUC) of dex and lisdex(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))
- Compare time to reach maximum plasma concentration (Tmax) between lisdex and dex(Two consecutive days; blood will be collected at time points: 0, 2, 4, 6, 9 and 12 (hours))
- Compare maximum plasma concentration (Cmax) between lisdex and dex(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))
研究者
R.K.R.W. Wettstein
Principal investigator
Amsterdam UMC, location VUmc