Lisdexamfetamine's Effect In ADHD in the Brain and Cognition
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Lisdexamfetamine
Intervention description: Participants will be given either the study drug or placebo in tablet form. All participants will start with a 20 mg dose and will be titrated up to a 70 mg daily dose over 9 weeks. Participants between 12-18 years of age will be titrated in 10 mg increments and participants between 18-25 years of age in 10-20 mg increments.
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 12 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: ADHD; Attention Deficit Hyperactivity Disorder; Vyvanse; Lisdexamfetamine

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.