The Day-time Response Variation of (Lis)Dexamphetamine

NCT04946461 | Completed DMC FDA Drug

• 1 other identifier: NL77195.018.21
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Adhd

Keywords

Dexamphetamine; lisdexamphetamine; ADHD; QbTest; Pharmacokinetics and dynamics

Outcome Measures

Primary Outcomes (8)

• Quantified behavior Test (QbTest)

  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).

  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)

• Drug Effects Questionnaire (DEQ)

  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.

  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)

• Bond-Lader Visual Analog Scale (BL-VAS)

  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

  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)

• QbTest performance questionnaire

  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.

  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)

• systolic blood pressure (mmHg)

  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).

  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)

• Diastolic blood pressure (mmHg)

  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).

  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)

• Heart rate (heart beats per minute)

  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).

  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)

• Plasma concentration of D-amphetamine

  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.

  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 (3)

• 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 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)

• 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)

Other Outcomes (1)

• The Leeds Sleep Evaluation Questionnaire (LSEQ)

  Two consecutive days; the LSEQ will only be conducted at baseline (T0) for each study day

Study Arms (2)

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.

Drug: Dexamfetamine Sulfate 5 Mg Oral Tablet; Drug: Lisdexamfetamine Dimesylate; Biological: blood samples

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.

Drug: Dexamfetamine Sulfate 5 Mg Oral Tablet; Drug: Lisdexamfetamine Dimesylate; Biological: blood samples

Interventions

Dexamfetamine Sulfate 5 Mg Oral Tablet DRUG

The dosage is set based on the recommendation of the practitioner. Dexamphetamine is administered twice a day, with an interval of 4 hours.

Also known as: Tentin

group 1; lisdex - dex; group 2; dex - lisdex

Lisdexamfetamine Dimesylate DRUG

The dosage is set based on the recommendation of the practitioner. Lisdexamphetamine is only administered once a day.

Also known as: Elvanse

group 1; lisdex - dex; group 2; dex - lisdex

blood samples BIOLOGICAL

The blood samples will be taken at set times: 0, 2, 4, 6, 9 and 12 (hours)

Also known as: vena puncture

group 1; lisdex - dex; group 2; dex - lisdex

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• No diagnosis for ADHD
• Currently other psychopharmacotherapy treatment than dex or lisdex
• Currently other psychopharmacotherapy parallel to dex or lisdex

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• ADHDcentraal: collaborator

Study Sites (1)

ADHDcentraal

Amsterdam, North Holland, 1043CB, Netherlands

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

A total of 12 blood samples (2 ml per sample) per subject will be taken.

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Amphetamine; Tablets; Lisdexamfetamine Dimesylate; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Dextroamphetamine; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• R. Mathot, PhD

  AUMC, location AMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: June 30, 2021
• Study Start: July 1, 2021
• Primary Completion: December 30, 2021
• Study Completion: June 16, 2022
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Within 1 year.
• Access Criteria: The relevant IPD can be requested through the website of ADHDcentraal.

Locations

NL (1)