Targeting Dopamine Therapy in RLS

Neurons in the brain require blood and oxygen for proper function. The term "neurovascular coupling" has been postulated in the 19th century by Roy & Sherrington referring to increased blood flow to active neurons. The rationale of this research relies on the neurovascular coupling, suggesting that increased blood flow to active regions on the brain should supply not only more blood, but also more of a pharmacological agent present in the blood system at the time. Thus, active regions should be affected by the agent (=drug) to a greater extent.

In the present study we focus on the dopaminergic system, critical in many functions such as cognition, response to stimuli and movement. One of the well-known dopaminergic pathways in the brain is the nigrostriatal pathway, mediating motor function. In this research, we intend to examine the effects of coupling functional activation in this pathway with a dopaminergic agent, Carbidopa/Levodopa, on symptoms of Restless Leg Syndrome (RLS). RLS is characterized by an irresistible urge to move the limbs (i.e. Akathisia), and results most prominently by a significant decrease in the quality of sleep. Our research focuses on this symptom of RLS to examine the effect of coupling brain activation and drug treatment.

The first line of treatment in RLS is dopaminergic drugs. These drugs increase dopamine levels in motor pathways, and our research will aim to couple activation in the nigrostriatal motor pathway with dopaminergic treatment in RLS. Functional activation will be achieved with a simple motor task, known to elicit activation in the nigrostriatal pathway. We hypothesize that the drug will act upon the pre-activated motor system, and that this coupling between brain activation and drug treatment will ameliorate sleep-related symptoms of RLS, compared with treating these symptoms solely with a dopaminergic drug and compared with using a non-motor task.

Study Overview

• Status: Unknown
• Conditions: Restless Legs Syndrome
• Intervention / Treatment: Drug: Placebo pill; Behavioral: Motor Task; Drug: Levodopa tablet; Behavioral: Sham non-motor task

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • N/A = Not Applicable
    • Tel Aviv, N/A = Not Applicable, Israel, 64288
      • Tel Aviv Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

RLS diagnosis according the common clinical criteria No known neurological illnesses No known Kidney illnesses No known iron deficiency No history of drug or alcohol use

Exclusion Criteria:

Regular drug treatment Use of a psychotropic substance in the two weeks prior to the study Auditory or Visual impairment Psychiatric history Neurological illness Chronic Kidney illness Obstructive Sleep Apnea (OSA) Dopaminergic drug intolerance or sensitivity Glaucoma Melanoma or Pre-Melanoma (current or previous) Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug + motor task; Each participant will undergo physical examination by an doctor. Then, the participant will receive the Fitbit device with instructions for proper use. The next stages will take place at the participant's home environment. Each participant will monitor motor activity in hours prior to sleep and at night for assessing baseline activity level. After 3 nights of monitoring, each participant will be administered with a quarter of a Dopicar pill (4th night) and half a Dopical pill (5th night), measuring different dose effect on motor activity during sleep.This group will be administered with a quarter of a Dopicar pill, 1 hour prior to sleep. After 15 minutes, participants in this group will perform a motor task (e.g., walking) for 30 minutes.	Behavioral: Motor Task; A motor task executed for 30 minutes after drug adminidtration; Drug: Levodopa tablet
Placebo Comparator: Placebo + motor task; Each participant will undergo physical examination by an doctor. Then, the participant will receive the Fitbit device with instructions for proper use. The next stages will take place at the participant's home environment. Each participant will monitor motor activity in hours prior to sleep and at night for assessing baseline activity level. After 3 nights of monitoring, each participant will be administered with a quarter of a Dopicar pill (4th night) and half a Dopical pill (5th night), measuring different dose effect on motor activity during sleep. This group will be administered with a quarter of a Placebo pill, 1 hour prior to sleep. After 15 minutes, participants in this group will perform a motor task (e.g., walking) for 30 minutes.	Drug: Placebo pill; Behavioral: Motor Task; A motor task executed for 30 minutes after drug adminidtration
Sham Comparator: Dopicar + Sham task; Each participant will undergo physical examination by an doctor. Then, the participant will receive the Fitbit device with instructions for proper use. The next stages will take place at the participant's home environment. Each participant will monitor motor activity in hours prior to sleep and at night for assessing baseline activity level. After 3 nights of monitoring, each participant will be administered with a quarter of a Dopicar pill (4th night) and half a Dopical pill (5th night), measuring different dose effect on motor activity during sleep. This group will be administered with a quarter of a Dopicar pill, 1 hour prior to sleep. After 15 minutes, participants in this group will perform a non-motor task (e.g., crossword puzzle) for 30 minutes.	Drug: Levodopa tablet; Behavioral: Sham non-motor task; A non-motor task )sham condition) will be executed for 30 minutes after drug adminidtration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Nighttime measures of motor activity will be used to assess the efficacy of treatment intervention	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reported efficacy	Participant's reports of the quality of sleep will be recorded	1 week

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): January 1, 2016

Study Registration Dates

• First Submitted: September 3, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimate): September 9, 2013

Study Record Updates

• Last Update Posted (Estimate): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: TASMC-13-TH-0416-CTIL