Study To Assess The Clinical Benefit Of Droxidopa In Subjects With Chronic Fatigue Syndrome
Condition: Chronic Fatigue Syndrome; Orthostatic Hypotension; Neurally Mediated Hypotension; Neurogenic Orthostatic Hypotension
MeSH terms: Fatigue Syndrome, Chronic; Hypotension, Orthostatic; Hypotension; Syndrome; Fatigue
Intervention: Droxidopa
Intervention description: 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
Intervention MeSH terms: Droxidopa
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: chronic fatigue syndrome; CFS; neurally mediated hypotension; NMH; neurogenic orthostatic hypotension; NOH; orthostatic hypotension; droxidopa

Summary:

      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.
    

Eligibility 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.]