Study To Assess The Clinical Benefit Of Droxidopa In Subjects With Chronic Fatigue Syndrome (CFS201)
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.
Chronic Fatigue Syndrome
Neurally Mediated Hypotension
Neurogenic Orthostatic Hypotension
|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|
- 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 ]
- 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 ]
|Study Start Date:||July 2010|
|Study Completion Date:||October 2011|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
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
Hide Detailed Description
This is a phase II, single-center, open-label study to evaluate the efficacy and safety of droxidopa in subjects with chronic fatigue syndrome. The study will enroll enough subjects to allow 10 to be placed in the 12 week open label treatment period.
The study will consist of an initial screening period (up to 7 days) to confirm eligibility followed by an up to 2 week dose titration period, a 12 week treatment period and a 30 day follow up period to account for any new or on-going AEs. During the screening visit the following assessments will be recorded:
- Medical history;
- Physical examination;
- Vital signs (BP, HR, weight)
- Stand Test (measurement of BP and heart rate in the supine position (head and torso elevated at approximately 30° from horizontal) 10, 5, immediately before and 1, 5 and 10 minutes after standing);
- Tilt Table Test
- Blood samples for hematology and biochemistry;
- Urine sample for urinalysis
- Pregnancy test for females of child bearing potential.
- Concomitant medication review o Subjects taking ephedrine or midodrine will stop taking these drugs for at least 7 days before the baseline assessments.
Within 7 days of successful screening, the following baseline assessments will be recorded:
- Inclusion/Exclusion review;
- Standing test (measurement of BP and heart rate 10, 5, immediately before and 1, 5 and 10 minutes after standing);
- Vital signs (BP, HR, and weight);
- Urine/serum pregnancy test for WOCP;
- Concomitant medications;
- Adverse events
- Multidimensional Fatigue Inventory (MFI);
- Brief Pain Inventory (BPI);
- Clinical Global Impression of Severity (CGI-S);
- Hospital Anxiety and Depression Scale (HADS);
- Patient Global Impression of Improvement (PGI-I).
Following successful completion of screening and baseline procedures, subjects will enter the dose titration period. Subjects will be titrated upwards by 100 mg TID, preferably on consecutive days but definitely within 14 days of entry, until one of the following 3 criteria for ceasing dose escalation is met:
- The subject has a sustained SBP of greater than 140 mmHg or DBP of greater than 90 mmHg after 1, 5 or 10 minutes of standing, OR a sustained SBP greater than 150 mmHg or DBP greater than 100 mmHg measured in the supine position (head and torso elevated at approximately 30° from horizontal).
- The subject is unable to tolerate side effects believed to be related to the study medication;
- The subject reaches the maximum dose of 600 mg TID droxidopa. If a subject meets criteria 1 they will proceed directly to the treatment period at the previous lower dose. Subjects meeting criteria 2 will also proceed directly to the treatment period at the previous lower dose. Subjects meeting criteria 3 will enter immediately into the treatment period at 600 mg TID.
Subjects that meet criteria 1 or 2 at the initial 100 mg TID dose will be considered baseline failures.
During treatment, the investigator can determine whether to modify the subject's dose. This determination will be based on the subject's tolerability of droxidopa.
Upon successful completion of the dose titration, subjects will begin a 12 week treatment period. Subjects will return to the clinic every 4 weeks (+/- 3 days) for efficacy, safety and compliance check. A follow-up call will occur 30 days after completion or removal of the trial to record any new or on-going AEs.
droxidopa [also, known as L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS] is the International non-proprietary name (INN) for a synthetic amino acid precursor of norepinephrine (NE), which was originally developed by Sumitomo Pharmaceuticals Co., Limited, Japan. It has been approved for use in Japan since 1989.
Droxidopa has been shown to improve symptoms of orthostatic hypotension that result from a variety of conditions including Shy Drager syndrome (Multiple System Atrophy), Pure Autonomic Failure, and Parkinson's disease. There are four stereoisomers of DOPS; however, only the L-threo-enantiomer (droxidopa) is biologically active.
The exact mechanism of action of droxidopa in the treatment of symptomatic NOH has not been precisely defined; however, its NE replenishing properties with concomitant recovery of decreased noradrenergic activity are considered to be of major importance.
Droxidopa has been marketed in Japan since 1989. Data from clinical studies and post-marketing surveillance programs conducted in Japan show that the most commonly reported adverse drug reactions with droxidopa are increased blood pressure, nausea, and headache. In clinical studies, the prevalence and severity of droxidopa adverse effects appear to be similar to those reported by the placebo control arm.
|United States, North Carolina|
|7421 Carmel Executive Park Drive, Ste. 320|
|Charlotte, North Carolina, United States, 28226|
|Principal Investigator:||Charles W Lapp, M.D.||Hunter-Hopkins Center, P.A.|