Clinical trial NCT02170298: Lisdexamfetamine's Effect In ADHD in the Brain and Cognition
Official title: Effects of Lisdexamfetamine on Cognitive Control and Reward Response in Adolescents and Young Adults With ADHD: Neural and Clinical Outcomes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: ADHD
Attention Deficit Hyperactivity Disorder
Vyvanse
Lisdexamfetamine
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2014-06-23
Enrollment: 6
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to identify the effects of lisdexamfetamine (LDX) on the neural and behavioral subcomponents of self-control, that is cognitive control and reward functioning, in adolescents and young adults with attention-deficit/hyperactivity disorder.

The investigators hypothesize that LDX is associated with 1a) decreased task-independent locus coeruleus (LC) activity; 1b) increased task-related activity in LC and the cognitive control network; 2) increased LC connectivity with the cognitive control network and 3) improved task performance and self-control. The investigators will test their hypotheses on fMRI data with linear contrasts of voxel-wise maps of parameter estimates (in both univariate and connectivity analyses).

The investigators will also assess change in brain activity with the LDX in the LC and ventral tegmental areas (VTA) as we hypothesize that they are altered in ADHD and related to cognitive control and self-control dysfunction in ADHD.

The investigators will use a repeated-measures, between-subject design to compare the effects of oral once daily LDX in a double-blind placebo-controlled randomized trial (RCT) on neural (fMRI) and behavioral correlates of cognitive control via a working memory and a reward - delay discounting task in adolescents and young adults.

A new condition has been added which will use a within-subject comparison, cross-over design between a single dose of LDX versus a single dose of placebo.


Eligibility criteria: Inclusion Criteria:

1. The subject is a male or female adolescent or young adult, between the ages of 12 and 30 (inclusive) at the time of the initial signing of the informed consent/assent
2. The subject meets DSM Fifth edition (DSM-5) diagnostic criteria for Attention Deficit-Hyperactivity Disorder, Combined-Type. Diagnostic Interviews and Rating Scales will be used to inform about DSM criteria. Participants with 4 or 5 hyperactive/impulsive symptoms may be included at the investigator's discretion.
3. This includes a history of childhood symptoms of ADHD for the adult subjects
4. The subject, a caregiver, and the investigator must all agree that the present ADHD symptoms cause impairment in the subject's normal routines, which include academic achievement, occupational functioning, social activities, and/or relationships
5. Females of childbearing potential (defined by menarche and not having undergone surgical sterilization/hysterectomy) must have a negative pregnancy test, must be practicing acceptable methods of contraception (or can confirm abstinence at each scheduled visit), and must not be pregnant or lactating at any point while they are participating in the study.
6. Written informed consent must be obtained from a legally acceptable representative (e.g. guardian or caregiver for minors), in accordance with requirements of the Institutional Review Board (IRB), prior to the initiation of any protocol-required procedures. In addition, the subject, as required by the IRB, must provide informed assent at screening and as such must be able to understand that he or she can withdraw from the time at any time.
7. The subject and the designated guardian(s) or caregiver(s)\[If minors\] are able to comprehend and satisfactorily comply with the protocol requirements, as evaluated by the investigator

Exclusion Criteria:

* Clinical contraindications

  1. History of schizophrenia, bipolar disorder, autism spectrum disorder, specific or focal neurological disorder
  2. Current academic learning disorder(s)
  3. Abnormal cardiac functioning with be excluded
  4. The subject experiences Adverse Events during the trial that would, in the investigator's judgment, preclude further exposure to LDX
  5. The subject had protocol violations during the trial considered major in the judgment of the investigator (significant noncompliance, use of prohibited concomitant medications, concern with use of drugs of abuse, etc.), which would deem them poor candidates for this trial
  6. Sexually active males who will not commit to utilizing an approved birth control methods or who will not remain abstinent during the trial and for 90 days following the last dose of study drug. Sexually active females of childbearing potential who will not commit to utilizing 1 of the approved birth control methods or who will not remain abstinent during the trial and for 30 days following the last dose of study drug. Abstinence will be permitted if it is confirmed and documented at every trial visit. If employing birth control, 1 of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injections, implant, condom or sponge with spermicide.
  7. Subjects with an inability to swallow tablets or tolerate oral medication
  8. It is in the investigator's opinion that it is not in the subject's best interest to continue
  9. Contraindication for MRI scanning (e.g., metal implants, pacemakers, metal foreign bodies, pregnancy)
* Beast-feeding (if applicable)

  1. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving trial drug
* Excluded medications

  1. Agents that lower blood levels of amphetamines: urinary acidifying agents (e.g. ammonium chloride, sodium acid phosphate, etc.); Methenamine Therapy.
  2. Agents that increase blood levels of amphetamines: urinary alkalinizing agents (e.g. Acetazolamide, some Thiazides).
  3. Dextroamphetamine is known to inhibit monoamine oxidase, as well as a metabolite of furazolidone. Concurrent administration of monoamine oxidase (MAOI) inhibitors is contraindicated because MAOIs potentially can result in hypertensive crisis. Vyvanse should not be given for at least 14 days after discontinuation of an MAO inhibitor.
  4. Agents whose effects may be reduced by amphetamines: Adrenergic blockers, Antihistamines, Antihypertensives, Veratrum Alkaloids, Ethosuximide.
  5. Agents whose effects may be potentiated by amphetamines: Tricyclic antidepressants, meperidine, Norepinephrine, Phenobarbital, Phenytoin.
  6. Agents that may reduce the effects of amphetamines: Antipsychotics, Lithium Carbonate
* Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation

  1. Previous negative history with LDX
* Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

  1. A positive drug screen for cocaine or other drugs of abuse (excluding caffeine, nicotine or prescribed psychostimulants for ADD/ADHD)
  2. History of substance dependence or abuse disorder currently or within past 5 years.
* Recent serious illness requiring systemic treatment and/or hospitalization prior to entry.

Primary outcomes:
measure: Working Memory
timeFrame: Baseline, 9 weeks
measure: Delay Discounting
timeFrame: Baseline, 9 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis MIND Institute
state: California
Study officials:
affiliation: University of California, Davis
name: Julie B Schweitzer, PhD
role: PRINCIPAL_INVESTIGATOR
References: