Study To Assess The Clinical Benefit Of Droxidopa In Subjects With Chronic Fatigue Syndrome (CFS201)

This study has been terminated.
(Enrollment issues.)
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT00977171
First received: September 11, 2009
Last updated: May 8, 2012
Last verified: May 2012
  Purpose

A subset of patients suffering from chronic fatigue syndrome exhibit symptoms of neurally mediated hypotension. While the underlying pathophysiology of chronic fatigue syndrome is not precisely understood, a dysfunction of the autonomic nervous system is thought to play a role in this subset of patients. In several small studies, subjects within this subset have noted improvement in their chronic fatigue symptoms when treated for their neurally mediated hypotension. As droxidopa acts on the autonomic nervous system and has been shown to ameliorate symptoms of neurally mediated hypotension, it is hypothesized that droxidopa could aid in the treatment of chronic fatigue symptoms.

Neurally mediated hypotension has been associated with patients suffering from chronic fatigue syndrome. Droxidopa meanwhile has been approved in Japan for the treatment of the symptoms of neurogenic orthostatic hypotension. As such, it is hypothesized that regulating the autonomic nervous system in patients with Chronic fatigue syndrome may prove to be clinically beneficial.


Condition Intervention Phase
Chronic Fatigue Syndrome
Orthostatic Hypotension
Neurally Mediated Hypotension
Neurogenic Orthostatic Hypotension
Drug: Droxidopa
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study To Assess The Clinical Benefit Of Droxidopa In Subjects With Chronic Fatigue Syndrome

Resource links provided by NLM:


Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • Evaluate the clinical efficacy, as determined by change in Patient Global Impression of Improvement, of droxidopa in patients with chronic fatigue syndrome in association with neurally mediated hypotension or neurogenic orthostatic hypotension. [ Time Frame: Baseline to end of 12 week treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Multidimensional Fatigue Inventory (MFI) [ Time Frame: baseline to end of Week 12 treatment period ] [ Designated as safety issue: No ]
  • Brief Pain Inventory (BPI) [ Time Frame: baseline to end of Week 12 treatment period ] [ Designated as safety issue: No ]
  • Clinical Global Impression of Severity (CGI-S) [ Time Frame: baseline to end of Week 12 treatment period ] [ Designated as safety issue: No ]
  • Hospital Anxiety and Depression Scale (HADS) [ Time Frame: baseline to end of Week 12 treatment period ] [ Designated as safety issue: No ]
  • Changes in Systolic blood pressure (SBP) and diastolic blood pressure (DBP): supine (head and torso elevated at approximately 30° from horizontal) measurements 10, 5, immediately before and 1, 5 and 10 minutes after standing. [ Time Frame: baseline to end of Week 12 treatment period ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: July 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Droxidopa Drug: Droxidopa
Oral, 100, 200, 300, 400, 500, or 600 mg TID, duration includes up to a 2 week titration period followed by a 12 week treatment period
Other Names:
  • L-threo-3,4-dihydroxyphenylserine
  • L-threo-DOPS
  • L-DOPS

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

SUBJECT SELECTION CRITERIA:

  • Female and male outpatients between 18-65 years of age;
  • Subjects must be diagnosed with chronic fatigue syndrome (Per Fukuda Criteria);
  • Subjects must have neurally mediated hypotension (NMH) or neurogenic orthostatic hypotension (NOH) (confirmed via Tilt table test);
  • Voluntarily read and sign an informed consent.

MAIN SUBJECT EXCLUSION CRITERIA:

  • Taking a direct acting vasoconstricting agent (i.e. ephedrine or midodrine)

    - Patients taking vasoconstrictor agents such as ephedrine, or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit (Visit 2);

  • Taking anti-hypertensive medication for the treatment of high blood pressure
  • Women of childbearing potential who are not using a medically accepted contraception;
  • Subject Restrictions: Reproductive potential: Female subjects should be either post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception throughout the study period and for 4 weeks after the last dose of investigational product. Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If hormonal contraceptives are used they should be taken according to the package insert. WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 4 weeks after the last dose of investigational product.
  • For WOCP a urine pregnancy test must be conducted at screening, baseline and study termination; the results must be negative at screening and at baseline. Any positive result will be confirmed by serum beta HCG pregnancy test.
  • Sexually active males whose partner is a WOCP must agree to use condoms for the duration of the study and for 4 weeks after the last dose;
  • Women who are pregnant, breast feeding, or plan to become pregnant during the course of this study;
  • Have a history of closed angle glaucoma;
  • Have uncontrolled supine hypertension, defined as systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg or use of ≥2 antihypertensive medications;
  • Have atrial fibrillation or, in the investigator's opinion, have any other significant cardiac arrhythmia;
  • Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
  • History of substance abuse or dependence within the past two years, excluding nicotine and caffeine.
  • Have a history of more than moderate alcohol consumption; (drinking in moderation is defined as having no more than 1 drink per day for women and no more than 2 drinks per day for men. This definition is referring to the amount consumed on any single day and is not intended as an average over several days)
  • Known or suspected hypersensitivity to the study medication or any of its ingredients;
  • Serious unstable medical illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, 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 who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
  • Subjects who are judged before randomization to be at suicidal risk by the clinical investigator.
  • Have diabetes mellitus or insipidus;
  • Have a known or suspected current malignancy. Patients with a history of cancer must be symptom- and treatment-free for at least 5 years before randomization, with the exception of patients with non-melanoma, non-invasive skin cancers (such as basal cell carcinoma), who should not have had an intervention or recurrence within one year of starting the study;;
  • Have known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug;
  • In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing;
  • Have a serum creatinine level >1.3 mg/ml
  • In the investigator's opinion, are unable to stand up without human or physical assistance;
  • Conditions that Exclude a Diagnosis of CFS
  • Any active medical condition that may explain the presence of chronic fatigue, such as untreated hypothyroidism, sleep apnea and narcolepsy, and iatrogenic conditions such as side effects of medication.
  • Persistence of unresolved or relapsing condition that could explain the presence of chronic fatigue, Examples of illnesses that can present such a picture include some types of malignancies and chronic cases of hepatitis B or C virus infection.
  • Any past or current diagnosis of a major depressive disorder with psychotic or melancholic features such as; bipolar affective disorders; schizophrenia of any subtype; delusional disorders of any subtype; dementias of any subtype; anorexia nervosa; or bulemia nervosa.
  • Alcohol or other substance abuse, occurring within 2 years of the onset of chronicfatigue and any time afterwards.
  • Severe obesity as defined by a body mass index [body mass index = weight in kilograms ÷ (height in meters)2] equal to or greater than 45. [Note: body mass index values vary considerably among different age groups and populations. No"normal" or "average" range of values can be suggested in a fashion that is meaningful. The BMI range of 45 or greater was selected because it clearly falls within the range of severe obesity.]
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00977171

Locations
United States, North Carolina
7421 Carmel Executive Park Drive, Ste. 320
Charlotte, North Carolina, United States, 28226
Sponsors and Collaborators
Chelsea Therapeutics
Investigators
Principal Investigator: Charles W Lapp, M.D. Hunter-Hopkins Center, P.A.
  More Information

No publications provided

Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT00977171     History of Changes
Other Study ID Numbers: Droxidopa CFS201
Study First Received: September 11, 2009
Last Updated: May 8, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Chelsea Therapeutics:
chronic fatigue syndrome
CFS
neurally mediated hypotension
NMH
neurogenic orthostatic hypotension
NOH
orthostatic hypotension
droxidopa

Additional relevant MeSH terms:
Fatigue
Fatigue Syndrome, Chronic
Hypotension
Hypotension, Orthostatic
Signs and Symptoms
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Encephalomyelitis
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Droxidopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014