Effectiveness of the Non-Stimulant Medication Lobeline in Improving Symptoms of Attention Deficit Hyperactivity Disorder in Adults - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00664703

Purpose

The study will evaluate the effectiveness of the nonstimulant medication lobeline in improving symptoms of attention deficit hyperactivity disorder in adults.

Condition	Intervention	Phase
Attention Deficit Disorder With Hyperactivity	Drug: Lobeline Placebo Drug: Lobeline Mid Dose Drug: Lobeline Low Dose Drug: Lobeline High Dose Drug: Methylphenidate Low Dose Drug: Methylphenidate High Dose Drug: Methylphenidate Placebo	Phase II

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder Mental Health

Drug Information available for: Methylphenidate hydrochloride Methylphenidate Dopamine Dopamine hydrochloride Lobeline Lobeline sulfate

U.S. FDA Resources

Study Type:

Interventional

Study Design:

Treatment, Randomized, Double Blind (Subject, Investigator), Factorial Assignment, Efficacy Study

Official Title:

A Double-Blind, Placebo-Controlled, Dose Ranging Study of 7.5, 15, and 30 mg of Sublingual Lobeline in Adult ADHD Patients

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Attention as measured by Conners' Continuous Performance Tests (CPT) [ Time Frame: Measured at Lab Visits 1 through 7 ] [ Designated as safety issue: No ]
Impulsivity as measured by Conners' CPT [ Time Frame: Measured at Lab Visits 1 through 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Working memory [ Time Frame: Measured at Lab Visits 1 through 7 ] [ Designated as safety issue: No ]
Subjective effects [ Time Frame: Measured at Lab Visits 1 through 7 ] [ Designated as safety issue: No ]
Cardiovascular effects [ Time Frame: Measured at Lab Visits 1 through 7 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:

15

Study Start Date:

July 2008

Estimated Study Completion Date:

September 2008

Estimated Primary Completion Date:

August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will take one pill of placebo lobeline or methylphenidate and one pill of active lobeline or methylphenidate on 7 separate days. Drug combinations and doses will vary each day.	Drug: Lobeline Placebo One placebo pill Drug: Lobeline Mid Dose One 15-mg lobeline pill Drug: Lobeline Low Dose One 7.5-mg lobeline pill Drug: Lobeline High Dose One 30-mg lobeline pill Drug: Methylphenidate Low Dose One 15-mg methylphenidate pill Drug: Methylphenidate High Dose One 30-mg methylphenidate pill Drug: Methylphenidate Placebo One placebo pill

Detailed Description:

Attention deficit hyperactivity disorder (ADHD) affects approximately 8 million adults in the United States. Adults with ADHD may experience difficulty concentrating, poor organization ability, mood swings, and trouble completing work. If not managed properly, ADHD can lead to behavioral, emotional, academic, social, and work-related problems. Neurobiological research has shown that people with ADHD exhibit low levels of dopamine, a neurotransmitter of the brain that controls a person's ability to concentrate and focus on surroundings. Lobeline, a nonstimulant medication that acts to alter dopamine uptake, may be effective in improving abnormalities in brain dopamine levels. Although lobeline has been successfully used as a smoking cessation aid because of its ability to inhibit nicotine-induced hyperactivity, the effectiveness of lobeline as a treatment for ADHD has not been explored. This study will evaluate the effectiveness of lobeline in improving adult ADHD symptoms, specifically inattention, impulsivity, and memory problems. This study will also evaluate any side effects of lobeline treatment.

Participation in this study will last between 4 and 5 weeks, during which participants will attend 10 study visits at the General Clinical Research Center (GCRC). Participants will first undergo a medical evaluation visit that will include a physical exam, electrocardiogram (EKG), blood draw, urine testing, and breath sampling. Participants will then return for an orientation visit to complete questionnaires and to receive training on the computer and on memory tasks to be performed during later visits.

The next 7 visits will comprise the laboratory testing and medication treatment portion of the study. Each visit will last 4.5 hours and will include urine and breath sampling, computer and memory tasks, questionnaires, vital sign measurements, and medication distribution. Participants will be randomly assigned to take two different pills at each lab visit. One pill will be a placebo of lobeline or methylphenidate, a medication stimulant used in treating ADHD, and the other pill will be active lobeline or methylphenidate. Drug combinations and doses will vary each day, but participants will never receive two active pills on the same day. All participants will undergo a follow-up evaluation between 7 and 14 days after the final lab visit. The evaluation will include questions about side effects from study medication, breath and urine sampling, a blood draw, and a physical exam.

Eligibility

Ages Eligible for Study:

21 Years to 45 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

History and current symptoms of ADHD as measured by the Structured Clinical Interview (SCID) for DSM-IV and supplemented with ADHD symptoms from the Kiddie-Schedule for Affective Disorders and Schizophrenia - Epidemiological (KSADS-E) Version, the Conners' Adult ADHD Rating Scale (CAARS), and the Adult ADHD Investigator Symptom Report Scale (AISRS)
Willing to use birth control
Body mass index (BMI) between 18 and 30
Not currently in the follow-up period of a preceding drug research study
No medical contraindications. See study appendix for full list of requirements.
Negative drug test (e.g., barbiturates, benzodiazepines, amphetamines, opiates, cocaine, cannabinoids, ethanol) at screening and at each laboratory day
Negative pregnancy test at screening and prior to each study drug administration, if female

Exclusion Criteria:

Recent history of drug addiction, alcoholism, and/or nicotine dependence
Any medical condition that could relapse during or immediately after the study and may interfere with study evaluations or affect a participant's safety
Significant acute or chronic medical disease
Blood pressure higher than 160/100 mmHg or lower than 90/40 mmHg
Heart rate more than 120 beats per minute (bpm) or less than 40 bpm while at rest, obtained on two consecutive measures over 15 minutes
Likely to need concomitant treatment medication during the study period
Alcohol consumption averaging more than 40 grams daily during the 30 days prior to study entry
Coffee or tea consumption greater than 6 cups per day or xanthine containing drink consumption greater than 1 liter per day
Without adequate means of contacting the investigator in case of emergency or not able to be contacted readily by the investigator
Female who is pregnant, breastfeeding, or plans to become pregnant during the study period or within 1 month after study drug administration
Exposure to any investigational new drug within 30 days of study entry
Regular use of any prescription or over-the-counter drugs
Use of any herbal products likely to induce or inhibit hepatic microsomal enzyme cytochrome P450 2D6 (CYP2D6) within 1 month of study entry, including St. John's wort (Hypericum perforatum)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664703

Contacts

Contact: Heather Synder, PhD	610-975-9290 ext 304	Heather@yaupontherapeutics.com
Contact: John Ranseen		jransee@email.uky.edu

Locations

United States, Kentucky
General Clinical Research Center, University of Kentucky	Recruiting
Lexington, Kentucky, United States, 40506
Principal Investigator: Catherine A. Martin, MD
Sub-Investigator: John Ranseen, PhD
Sub-Investigator: Sharon Walsh, PhD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Catherine A. Martin, MD

University of Kentucky Department of Psychiatry

More Information

Responsible Party:

Yaupon Therapeutics, Inc. ( Robert Alonso, President & CEO )

Study ID Numbers:

R43 MH081553, DATR BT-BU, 2007LOBADHD-201-US, 7-0432-F2L

First Received:

April 21, 2008

Last Updated:

July 1, 2008

ClinicalTrials.gov Identifier:

NCT00664703

Health Authority:

United States: Food and Drug Administration

Keywords provided by National Institute of Mental Health (NIMH):

Dopamine Uptake Inhibitors
Dopamine
Methylphenidate
Mental Disorders Diagnosed in Childhood

Neurologic Manifestations
Attention Deficit and Disruptive Behavior Disorders
Hyperkinesis
Dyskinesias

Study placed in the following topic categories:

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

Methylphenidate
Attention Deficit and Disruptive Behavior Disorders
Neurologic Manifestations
Hyperkinesis
Dyskinesias

Additional relevant MeSH terms:

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

Central Nervous System Stimulants
Cholinergic Agents
Pharmacologic Actions
Pathologic Processes
Autonomic Agents
Therapeutic Uses
Ganglionic Stimulants
Dopamine Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 07, 2009