Overview

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

Status:
Terminated
Trial end date:
2011-10-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Chelsea Therapeutics
Treatments:
Droxidopa
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.]