An In Depth Cardiovascular Study of Lisdexamfetamine (LDX; Vyvanse) in Healthy and Treated Hypertensive Adults With Attention Deficit Hyperactivity Disorder (ADHD) - Full Text View

Sponsors and Collaborators:	Massachusetts General Hospital Shire Pharmaceutical Development
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00753012

Purpose

The purpose of this research study is to learn about the effects of a medication called Vyvanse on the heart (cardiovascular system). The U.S. Food and Drug Administration (FDA) has approved Vyvanse for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). People who have ADHD have trouble paying attention, organizing, and planning; these symptoms can cause problems at work, socially and at home.

Vyvanse (also known as Lisdexamfetamine) is an amphetamine (a stimulant). Amphetamines increase alertness and activity. They are considered safe and effective for treating ADHD in children. Less is known about the safety and effectiveness of stimulants when they are used to treat adults with ADHD. There have been some reports of sudden death in children and adults treated with stimulants. There is no definite evidence that the deaths were related to the use of stimulants. However, the deaths have raised questions about the effects that stimulants might have on such things as blood pressure and heart rate.

The study will involve measuring your blood pressure both at home and in the office as well as cardiovascular tests at the main campus of MGH. The cardiovascular tests involved in the study are the echocardiograph (ultrasound of the heart) and cardiopulmonary exercise test (also called stress test; subjects exercise on a bicycle while measuring their heart activity and breathing is monitored by cardiologists).

We predict to see changes in blood pressure and heart rate (average increase of heart rate 3-7 bpm, 1-5 mmHg blood pressure) as shown in other clinical studies. We predict that cardiovascular tests, such as the stress test, will show higher resting heart rate and lower heart rate recovery during exercise on LDX in comparison to exercise off LDX. However, we do not expect to see any changes in heart and lung functioning on LDX as compared to off LDX.

Condition	Intervention	Phase
Attention Deficit/Hyperactivity Disorder(ADHD)	Drug: Lisdexamfetamine (LDX; Vyvanse)	Phase IV

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder Exercise and Physical Fitness

Drug Information available for: Lisdexamfetamine Lisdexamfetamine dimesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Open Label, Single Group Assignment
Official Title:	An In Depth Cardiovascular Study of Lisdexamfetamine (LDX; Vyvanse) in Healthy and Treated Hypertensive Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Changes in blood pressure, heart rate, and ECG parameters; BP and HR change over time as a function of LDX dose; episodes of hypertension; CPET and TTE measures on LDX at 6 months in comparison to baseline assessments. [ Time Frame: BP is measured at every visit; ECG is completed at Week 99, Week 6, & Week 11; CPET and TTE testing is completed prior to starting study medication and at the end of the subject's study participation. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	April 2008
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Adults who meet DSM-IV-TR criteria for ADHD. Group 1 is normotensive adults; Group 1 does not have high blood pressure. Group 2 is primary hypertensive adults; Group 2 does have high blood pressure and is being treated with stable doses of up to two FDA approved hypertensive medications achieving a stable blood pressure of <135/85. High blood pressure is defined as 140-159mmHg/90-99 mmHg.	Drug: Lisdexamfetamine (LDX; Vyvanse) Upon completion of screening procedures and meeting eligibility criteria, subjects will begin taking Lisdexamfetamine daily until the completion of participation in the clinical trial (up to Week 11 or final study visit). Subjects will start on 30 mg of LDX per day for the first week of treatment. The dose will be increased weekly in 20 mg increments, up to a 70 mg daily (maximum). If significant adverse effects (AE) occur, the daily dose may be reduced by 20 mg. At subsequent visits, a higher dose may be resumed if tolerated. Both cohorts of the study will follow the same treatment plan.

Arms

Assigned Interventions

1: Experimental

Adults who meet DSM-IV-TR criteria for ADHD.

Group 1 is normotensive adults; Group 1 does not have high blood pressure. Group 2 is primary hypertensive adults; Group 2 does have high blood pressure and is being treated with stable doses of up to two FDA approved hypertensive medications achieving a stable blood pressure of <135/85. High blood pressure is defined as 140-159mmHg/90-99 mmHg.

Drug: Lisdexamfetamine (LDX; Vyvanse)

Upon completion of screening procedures and meeting eligibility criteria, subjects will begin taking Lisdexamfetamine daily until the completion of participation in the clinical trial (up to Week 11 or final study visit). Subjects will start on 30 mg of LDX per day for the first week of treatment. The dose will be increased weekly in 20 mg increments, up to a 70 mg daily (maximum). If significant adverse effects (AE) occur, the daily dose may be reduced by 20 mg. At subsequent visits, a higher dose may be resumed if tolerated. Both cohorts of the study will follow the same treatment plan.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female outpatients 18-60 years of age.
A current DSM-IV-TR diagnosis of ADHD, confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) at Screening.
In phase two only; Stage I primary hypertension (SBP 140-159 mm Hg/DBP 90-99 mm Hg) as defined by Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (Chobanian et al, 2003).
In phase two only; Treatment with stable doses of up to two FDA approved antihypertensive medications achieving a stable blood pressure of <135/85. Acceptable classes of medications include diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or receptor blockers, aldosterone antagonists, calcium-channel blockers (Rosendorff et al, 2007).

Exclusion Criteria:

Pregnant or nursing females.
Clinically significant cardiovascular history, including angina, syncope, thrombosis, aneurysm, myocardial infarction, myocarditis, valvular disease, heart failure, or arrhythmia. Hypertension is exclusionary in phase one subjects.
In phase two; hypertension is not exclusionary, however blood pressure with antihypertensive treatment of ≥135/85 at baseline is exclusionary.
Clinically significant or unstable medical condition including pulmonary (asthma, edema, thrombosis), renal, hepatic, metabolic (thyroid) or neurological disorder, based upon a medical history.
Orthopedic impairment or BMI that significantly impacts or restricts exercise performance testing, per clinician judgment.
Any clinically unstable psychiatric conditions including suicidality, homicidality, bipolar disorder, psychosis.
Current (within 3 months) DSM-IV-TR criteria for current abuse or dependence with any psychoactive substance other than nicotine.
Ongoing treatment with any psychotropic medication, including anxiolytics, antidepressants, mood stabilizers.
Use of Monoamine Oxidase Inhibitors (MAOIs) including linezolid within two weeks prior to starting study medication.
Mental retardation (IQ < 75).
History of intolerance or allergy to LDX.
Diagnosis of glaucoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753012

Contacts

Contact: Meghan Kotarski, MBA		mkotarski@partners.org
Contact: Courtney Williams, BA		cgwilliams@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Cambridge, Massachusetts, United States, 02138
Contact: Meghan Kotarski, MBA mkotarski@partners.org
Contact: Courtney Williams, BA cgwilliams@partners.org
Principal Investigator: Paul Hammerness, MD

Sponsors and Collaborators

Massachusetts General Hospital

Shire Pharmaceutical Development

Investigators

Principal Investigator:

Paul Hammerness, MD

Massachusetts General Hospital

More Information

Responsible Party:	Massachusetts General Hospital ( Paul Hammerness, MD )
Study ID Numbers:	2008-P-000121
Study First Received:	September 12, 2008
Last Updated:	September 15, 2008
ClinicalTrials.gov Identifier:	NCT00753012
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

cardiovascular testing
home blood pressure monitoring
office home blood pressure monitoring
cardiopulmonary exercise testing

transthoracic echocardiography
Lisdexamfetamine
Vyvanse
normotensive and hypertensive adults with ADHD.

Study placed in the following topic categories:

Signs and Symptoms
Dopamine
Attention Deficit Disorder with Hyperactivity
Mental Disorders
Dextroamphetamine
Mental Disorders Diagnosed in Childhood

Neurologic Manifestations
Attention Deficit and Disruptive Behavior Disorders
Hyperkinesis
Healthy
Dyskinesias

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Disease
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs

Central Nervous System Stimulants
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009