Chronic Fatigue Syndrome

This study has been completed.
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
Joel L. Young, M.D., Rochester Center for Behavioral Medicine
ClinicalTrials.gov Identifier:
NCT01071044
First received: February 17, 2010
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

Over the past decade, the Rochester Center for Behavioral Medicine (RCBM) has evaluated many patients with attention deficit hyperactivity disorder (ADHD). A recurrent finding in these patients is a history of unexplained fatigue and musculoskeletal pain. Some of these patients have previously been identified by other treatment providers as having fibromyalgia syndrome (FMS) or chronic fatigue syndrome (CFS). Many of these patients have been evaluated within the traditional medical system, often by rheumatologists and neurologists. Others have been evaluated in non-traditional settings by chiropractors and nutritionists. Physicians shun these patients as their complaints are persistent. They are perceived to be malingering or opiate seeking. Many physicians will remark that they do not believe in these conditions. Rather uniformly, patients and their doctors are unhappy with the results of treatment. This dynamic is consistent with the experience of adult ADHD patients prior to the acceptance of this condition.

Treatment of these patients in our clinic has revealed that when their underlying ADHD is treated with psychostimulant medication, many patients report significant improvements with regard to their fatigue and musculoskeletal pain. Patients report less subjective fatigue and pain and note overall functional improvement, although the initial and primary objective was the treatment of their attention or hyperactivity problems. We speculate that stimulants are efficacious by offering two distinct clinical properties. 1) anti-fatigue properties and 2) properties that allow patients to filter out extraneous stimuli (i.e. chronic muscle pain).

As a result of these findings RCBM developed a chronic fatigue/fibromyalgia clinic in the early 2000's. This clinic was staffed by a board-certified rheumatologist and the psychiatric staff at RCBM. Through the major referral hospital in the area, patients with self-identified fibromyalgia and chronic fatigue were referred to our clinic. Over eighteen months, we evaluated 75 patients, and found that in patients who had comprehensive evaluations, nearly 70 percent also had a history of ADHD, inattentive or combined types. Diagnosis was made using clinical history and standardized symptom checklists. Oftentimes, the ADHD had been previously undiagnosed. This finding supports the link between ADHD and FMS/CFS.

Results from these evaluations reinforced our initial findings: patients who are treated for their ADHD symptoms also show a reduction in their chronic pain and fatigue symptoms. This is true regardless of previous (unsuccessful) therapies to treat their fibromyalgia.

As a result of these findings, we are conducting a controlled study to further demonstrate the efficacy of lisdexamfetamine dimesylate (LDX) in controlling fatigue symptoms in patients presenting with chronic fatigue syndrome. This is a double-blind, placebo-controlled study over a period of 8 weeks, where subjects are randomized to either LDX or placebo. We will evaluate subjects through standardized pain, fatigue and ADHD assessment scales.


Condition Intervention Phase
Chronic Fatigue Syndrome
Cognitive Impairments
Drug: Lisdexamfetamine Dimesylate
Drug: Placebo Comparator: Sugar pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Use of Lisdexamfetamine Dimesylate in Treatment of Cognitive Impairment (Chronic Fatigue Syndrome): A Double Blind, Placebo Controlled Study

Resource links provided by NLM:


Further study details as provided by Rochester Center for Behavioral Medicine:

Primary Outcome Measures:
  • The primary outcome measure will be the mean change from baseline to treatment week 6 of the Behavior Rating Inventory of Executive Functioning-Adult Version (BRIEF-A). [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare the change in the Fatigue Severity Scale (FSS) from baseline to week 6 between LDX and placebo treated patients. [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Compare the change in the Hamilton Anxiety scale from baseline to week 6 between LDX and placebo treated patients. [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Compare the change in the Brief Pain Inventory (BPI) Short Form from baseline to week 6 between LDX and placebo treated patients. [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Compare the change in the Short Form McGill Pain Questionnaire (SF-MPQ) from baseline to week 6 between LDX and placebo treated patients. [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Compare the change in the Fibromyalgia Impact Questionnaire (FIQ) from baseline to week 6 between LDX and placebo treated patients. [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Assess the prevalence of ADHD in this population using the Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Compare the change in the ADHD-RS from baseline to week 6 between LDX and placebo treated patients. [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Assess whether the presence of ADHD in patients in this population predicts treatment response. [ Time Frame: Every visit ] [ Designated as safety issue: No ]
  • Assess the prevalence of comorbidities in this population using the Adult Self-Report Inventory (ASRI-4). [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]
  • Compare the changes using the Clinical Global Impression of Severity Scale (CGI-S) from screening to week 6 between placebo and LDX treated patients. [ Time Frame: Every visit ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: November 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lisdexamfetamine Dimesylate
Subjects will be started with a single pill containing 30mg of LDX or comparable placebo, depending on the treatment assignment. At the week 2 visit, the dose will be increased to 50 mg (or comparable placebo) if the patient exhibits no significant adverse effects as judged by the Investigator. At the week 4 visit, the dose will be increased to 70 mg (or comparable placebo) if the patient exhibits no significant adverse effects as judged by the investigator.
Drug: Lisdexamfetamine Dimesylate
Will be randomly assigned to one of two treatment arms in a 1:1 ratio of either LDX or placebo for 6 weeks. Subjects will be started with a single pill containing 30mg of LDX or comparable placebo, depending on the treatment assignment. At the week 2 visit, the dose will be increased to 50 mg (or comparable placebo) if the patient exhibits no significant adverse effects as judged by the Investigator. At the week 4 visit, the dose will be increased to 70 mg (or comparable placebo) if the patient exhibits no significant adverse effects as judged by the investigator.
Placebo Comparator: Sugar pill Drug: Placebo Comparator: Sugar pill
Will be randomly assigned to one of two treatment arms in a 1:1 ratio of either LDX or placebo for 6 weeks. Subjects will be started with a single pill containing 30mg of LDX or comparable placebo, depending on the treatment assignment. At the week 2 visit, the dose will be increased to 50 mg (or comparable placebo) if the patient exhibits no significant adverse effects as judged by the Investigator. At the week 4 visit, the dose will be increased to 70 mg (or comparable placebo) if the patient exhibits no significant adverse effects as judged by the investigator.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • BRIEF-A Global Executive Composite score (GEC) ≥ 65, or Behavioral Regulation Index score (BRI) ≥ 65, or Metacognition Index score (MI) ≥ 65.
  • Subjects must meet consensus criteria for chronic fatigue syndrome. These criteria will be assessed by obtaining clinical histories and using appropriate symptom checklists.
  • Provide written informed consent for participation in the trial before completing any study-related procedures.
  • Are between the ages of 18 and 60, inclusive, at the time informed consent is obtained.
  • Male or non-pregnant females who are not breastfeeding. Females of reproductive potential must agree to use a medically accepted means of contraception when engaging in sexual intercourse at any time during the study. Females with childbearing potential who are abstinent may enter the study if they agree that they will use medically acceptable contraception should they should become sexually active during the study. Women of childbearing potential must test negative for pregnancy at the Screening Visit.
  • Are able to swallow study medication.
  • Have normal intelligence, are able to communicate effectively with the study team and are likely to fully comply with study procedures and restrictions, including all clinic visits and assessments required by the protocol.

Exclusion Criteria:

  • BRIEF-A Global Executive Composite score < 65, or Behavioral Regulation Index score (BRI) < 65, or Metacognition Index score (MI) < 65.
  • Immediate family of the Investigator or others directly affiliated with the study.
  • Received treatment with a drug that has not received regulatory approval or participated in a clinical trial within 30 days prior to screening.
  • Weigh less than 30 kg or greater than 120 kg at the time of informed consent, or in the opinion of the Investigator, are significantly underweight or morbidly obese.
  • Have a documented history of Bipolar I Disorder or any history of psychosis or pervasive developmental disorder. In addition, subjects with any comorbid psychiatric diagnosis with significant symptoms (severe Axis II disorder, or severe Axis I disorders such as post-traumatic stress disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorders) will be excluded. Subjects with mild to moderate Axis I disorders such as social phobia and dysthymia and ADHD may be included.
  • History of substance abuse or drug dependence according to DSM-IV-TRTM criteria currently or within one year prior to study participation, excluding nicotine and caffeine. This is determined through clinical history and symptom checklist to be obtained at visit 1.
  • Serious chronic or acute unstable medical condition or illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, narrow angle glaucoma, or other unstable medical or psychiatric conditions that in the opinion of the Investigator would compromise participation or would likely lead to hospitalization during the duration of the study. Subjects with a history of mental retardation or a severe learning disability are also excluded.
  • History of seizure disorder (other than infantile febrile seizures), any tic disorder, current diagnosis and/or family history of Tourette's disorder.
  • Subjects with a history of organic heart disease including coronary artery disease, past myocardial infarction, angina, arrhythmias, congestive heart failure, valvular heart disease and congenital heart disease.
  • Subject has a history of hypertension, unless controlled with a stable dose of blood pressure medication for a period of three months or more, or has a resting sitting systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg.
  • Patients who are taking any excluded medications that cannot be discontinued prior to beginning treatment with study medication.
  • Have a known hypersensitivity, allergy intolerance or documented history of non-responsivity to methylphenidate or amphetamine, to amphetamine-based medications, to LDX, or to any of its ingredients.
  • Subjects who, in the opinion of the Investigator, are unsuitable in any other way to participate in the study.
  • Subjects on duloxetine, bupropion or pregabalin.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01071044

Locations
United States, Michigan
Rochester Center for Behavioral Medicine
Rochester Hills, Michigan, United States, 48307
Sponsors and Collaborators
Rochester Center for Behavioral Medicine
Shire
Investigators
Principal Investigator: Joel L. Young, M.D. Rochester Center for Behavioral Medicine
  More Information

No publications provided

Responsible Party: Joel L. Young, M.D., Principal Investigator, Rochester Center for Behavioral Medicine
ClinicalTrials.gov Identifier: NCT01071044     History of Changes
Other Study ID Numbers: RCBM11
Study First Received: February 17, 2010
Last Updated: May 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Rochester Center for Behavioral Medicine:
Chronic Fatigue Syndrome

Additional relevant MeSH terms:
Fatigue
Fatigue Syndrome, Chronic
Cognition Disorders
Signs and Symptoms
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Encephalomyelitis
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dextroamphetamine
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014