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Sildenafil on its effects on Fatigue, Cerebral Blood Flow in ME/CFS

Discussion in 'Active Clinical Studies' started by Cort, Jun 15, 2009.

  1. Cort

    Cort Phoenix Rising Founder

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    Raleigh, NC
    (thanks to Tom Kindlon for providing this)

    http://clinicaltrials.gov/ct2/show/NCT00598585

    Use of Sildenafil to Alter Fatigue, Functional Status and Impaired Cerebral
    Blood Flow in Patients With CFS
    This study is currently recruiting participants.

    Verified by Charles Drew University of Medicine and Science, February 2009

    First Received: August 31, 2005
    Last Updated: February 23, 2009
    History of Changes
    Sponsors and Collaborators: Charles Drew University of Medicine and Science
    Pfizer

    Information provided by: Charles Drew University of Medicine and Science
    ClinicalTrials.gov Identifier: NCT00598585

    Purpose
    Use of Sildenafil to Alter Symptoms in Patients with Chronic Fatigue
    Syndrome (CFS)


    Condition Intervention Phase
    Chronic Fatigue Syndrome
    Drug: Sildenafil
    Drug: Placebo
    Phase IV



    MedlinePlus related topics: Chronic Fatigue Syndrome
    Drug Information available for: Sildenafil Sildenafil citrate
    U.S. FDA Resources
    Study Type: Interventional
    Study Design: Treatment, Randomized, Double Blind (Subject, Investigator),
    Placebo Control, Parallel Assignment, Efficacy Study
    Official Title: Phase 4 Study of the Use of Sildenafil to Alter Fatigue,
    Functional Status and Impaired Cerebral Blood Flow in Patients With Chronic
    Fatigue Syndrome.


    Further study details as provided by Charles Drew University of Medicine and
    Science:


    Primary Outcome Measures:

    .The principal aim of this study is to determine whether chronic fatigue
    syndrome (CFS) is due to inadequate blood flow to the brain and to test a
    medication, Sildenafil, which should help increase blood flow to the brain
    and improve the symptoms of CFS. [ Time Frame: 6 weeks ] [ Designated as
    safety issue: Yes ]


    Estimated Enrollment: 30
    Study Start Date: July 2002
    Estimated Study Completion Date: December 2010
    Estimated Primary Completion Date: December 2010 (Final data collection date
    for primary outcome measure)
    Arms Assigned Interventions
    1: Experimental
    Double Blind study- one group will be on Sildenafil and the other group will
    be on placebo. Drug: Sildenafil
    25 mg tid of either Sildenafil or Placebo for first week. 50 mg tid of
    either Sildenafil or Placebo for second week. 100 mg tid of either
    Sildenafil or Placebo for 3rd,4th, 5th and 6th week of study participation.

    2: Placebo Comparator Drug: Placebo
    Placebo


    Detailed Description:
    Use of Sildenafil to Alter Fatigue, Functional Status and Impaired Cerebral
    Blood Flow in Patients with Chronic Fatigue Syndrome.

    Eligibility


    Ages Eligible for Study: 18 Years to 49 Years
    Genders Eligible for Study: Both
    Accepts Healthy Volunteers: Yes

    Criteria
    Inclusion Criteria:

    .Patients meeting the CDC definition of CFS.
    .All races, ethnicities, socio-economic status (SES), and gender
    .Age greater than 18 (because of concerns about radioactivity, we and the
    Cedars-Sinai and Harbor-UCLA IRBs have decided not to enroll subjects below
    the age of 18).
    .Age less than 50. Because of concern of sildenafil exacerbating coronary
    artery disease, we will only enroll patients younger than 50.
    .Able to provide informed consent.
    .Willingness to be off all medicines and supplements for 3 weeks prior to
    the study.
    .Patients with psychiatric disorders (see below) will be included, if they
    could be off their medications, and if their psychiatric diagnosis clearly
    occurred after their fatigue symptoms began.
    .Patients with concurrent fibromyalgia will be allowed to participate if the
    meet diagnostic criteria for CFS.
    Exclusion Criteria:

    .Disabilities that would prevent them from participating in the study.
    .Current use of prescription medicines (starting at 3 weeks prior to the
    study) and supplements (starting at 1 weeks prior to the study) except
    acetaminophen or aspirin. This includes herbal supplements and vitamins.
    .Existing medical illnesses, such as heart disease, hypertension, cancer,
    rheumatological diseases, endocrinopathies or hormone replacement therapy,
    seizure disorders, severe obesity (BMI > 32 kg/m2),
    .Severe psychiatric disorders including bipolar disorder, schizophrenia,
    dementia and previous or current diagnosis of alcohol or substance abuse
    within the past year. Patients with depression of such severity as to
    warrant treatment with anti-depressants will be excluded.
    .Current abuse of illicit drugs or heavy ethanol use.
    .Pregnant women will be excluded because of radioactivity exposure from the
    SPECT scans.
    .Abnormal EKG
    .Abnormal CBC, blood chemistries, thyroid function tests, and HIV, ANA, RF
    and ESR tests.
    Contacts and Locations

    Please refer to this study by its ClinicalTrials.gov identifier: NCT00598585

    Contacts
    Contact: Erik Zuckerbraun, M.D. 310.668.8754 erikzuckerbraun@cdrewu.edu
    Contact: Christian Gastelum, M.D. 310.668.8754 christiangastelum@cdrewu.edu

    Locations
    United States, California
    Charles Drew University of Medicine and Science Recruiting
    Los Angeles, California, United States, 90059
    Contact: Erik Zuckerbraun, M.D. 310-668-8754 erzucker@cdrewu.edu

    Contact: Christian Gastelum, M.D. 310.668.8754
    Christiangastelum@cdrewu.edu
    Principal Investigator: Ted C Friedman, M.D., Ph.D.
    Sponsors and Collaborators
    Charles Drew University of Medicine and Science
    Pfizer
    Investigators
    Principal Investigator: Ted C Friedman, M.D., Ph.D. Charles Drew University
    of Medicine and Science

    More Information

    Additional Information:
    Clinical Trial Research site

    No publications provided

    Responsible Party: Charles Drew University of Medicine and Science (
    Theodore C. Friedman, M.D.,Ph.D. principal investigator )
    Study ID Numbers: 02-04-378-07
    Study First Received: August 31, 2005
    Last Updated: February 23, 2009
    ClinicalTrials.gov Identifier: NCT00598585 History of Changes
    Health Authority: United States: Institutional Review Board

    Study placed in the following topic categories:
    Vasodilator Agents
    Fatigue
    Central Nervous System Diseases
    Encephalomyelitis
    Sildenafil
    Fatigue Syndrome, Chronic
    Cardiovascular Agents
    Virus Diseases
    Signs and Symptoms
    Phosphodiesterase Inhibitors
    Muscular Diseases
    Musculoskeletal Diseases
    Neuromuscular Diseases
    Myalgic Encephalomyelitis



    Additional relevant MeSH terms:
    Vasodilator Agents
    Fatigue
    Disease
    Molecular Mechanisms of Pharmacological Action
    Nervous System Diseases
    Central Nervous System Diseases
    Enzyme Inhibitors
    Sildenafil
    Encephalomyelitis
    Cardiovascular Agents
    Fatigue Syndrome, Chronic
    Pharmacologic Actions
    Virus Diseases
    Signs and Symptoms
    Phosphodiesterase Inhibitors
    Muscular Diseases
    Pathologic Processes
    Musculoskeletal Diseases
    Neuromuscular Diseases
    Therapeutic Uses
    Syndrome



    ClinicalTrials.gov processed this record on June 11, 2009
     
  2. Jody

    Jody Senior Member

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    Aren't there concerns about some of the side effects that are possible with sildenafil though? The headaches, seeing blue (I know there's a proper term for this but can't remember :eek: ).

    I wonder sometimes about the tendency to throw drugs with potential side effects, as guesswork, at something that already has enough guesswork to it like CFS.

    I mean, there are the questions about low blood volume, and the lack of answers as to what causes it ... is it really ethical to take a chance with these patients as the pharmaceutical people do?

    This issue to me is not only about sildenafil, but is rather across the board in my mind.

    CFS patients are truly guinea pigs in alot of areas.
     
  3. Freddd

    Freddd Senior Member

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    Hi Jody,

    Here is a response out of the blue ...
    I suspect that it is being tried because of many anecdotal positive results. I found Sildenafil beneficial for all things neuropathic. However, due to the price it was only an occasional treat. However complying with the entry requirements would be devestating and possibly bring back many of the symptoms they are looking for. Now if they could roll back the clock 12 years ...
     
  4. Jody

    Jody Senior Member

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    Freddd,

    That is what I am thinking.

    It's great if it works for some people. I'm sure it does.

    I just hate to see it backfire on some of the guinea pigs ... er, test subjects.
     
  5. Freddd

    Freddd Senior Member

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    Hi Jody,

    Because of the desperation I felt I volunteered for some things, like phase III Stadol for chronic pain. It was a similar situation, an already approved drug with a known risk profile for a new use. It was the most effective thing I had short of morphine for pain and finally mb12 and adob12. The worst part was the redescent into severe pain for 11 more years after the study ended.
     
  6. Jody

    Jody Senior Member

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    Freddd,

    I understand your reasoning.

    Desperation can be a great motivator. Sometimes it even pays off. :)
     
  7. At first glance, I would imagine using ED drugs for this illness is a poor mans MIDODRINE? (That's a vasoconstrictor, which helps reduce blood pooling) often leading to quite dramatic increases in mobility levels in ME CFS for short periods of time.

    Problem is, it's not licensed and you have to get it as a special arrangement after an TILT test. Maybe using ED drugs was a way to try and get around this? I honestly don't know.

    Look MIDODRINE up if you're interested in combating Orthostatic Intolerance (OI), it's the only thing used for Dysautonomia/POTS that actually works, frustratingly it has horrible side effects - sadly not what ED drugs do.

    Having said that, it would be quite bizarre being able to walk upright - but be simutanteously priapic as a side effect, unless one was helping a plane park in an airport or something. I know in this illness ones nether regions are often terribly painful, and in ME CFS we are known to have an altered Nitric Oxide level - which these ED drugs affect as Nitric Oxide is important for arousal in men.

    Does that affect blood flow centrally, rather than peripherally?
    The side effects of ED are rather serious cardiac problems and hypertension. I personally would not go downing a blue pill and winking at the post mistress quite yet.

    I'd stick to MIDODRINE and a cardiologist who knows what they're doing in conjunction with an expert in Dysautonomia/Syncope. Having said that it would be interesting to learn more about the action of Nitric Oxide with this medication, in this illness specifically - due to the effects on blood vessels and 'smooth muscle'.

    Smooth muscle and it's cardiac actions (specifically) are affected by dilating of blood vessels due to excessive acetylcholine. Do ED drugs combat this, or actually encourage it?
     
  8. ramakentesh

    ramakentesh Senior Member

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    I think this study is the result of demonstration that CFS patients - even those that seem to 'pass' tilt table tests still have reduced cerebral perfusion.

    This may be why:

    http://cat.inist.fr/?aModele=afficheN&cpsidt=21791046

    In this case a parasympathetic deficit is presumed to be the cause? Either way it may be that some of these patients actually appeared normal on tilt.

    It also it being investigated because at least in some patients with OI there appears to be inappropriate arterial vasoconstriction that may be being caused by reduced neuronal nitric oxide levels:

    http://ajpheart.physiology.org/cgi/content/abstract/293/4/H2161

    http://www.circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.104.526764v1

    And kind of related in CFS:

    http://chronicfatigue.about.com/b/2...exercise-fatigue-chronic-fatigue-syndrome.htm

    Not all OI patients pool peripherally. many pool in their stomach circulation and a marge portion appear to suffer impaired cerebral-vascularl control due to inappropriate sympathetic or parasympathetic controls. Still some do have total arterial vasoconstriction which reduces venous return to the heart and OI symptoms.

    Not sure whether it will actually help but Id be interested to see the results.
     
  9. perovyscus

    perovyscus

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    Viagra is generally a vasodilator, and this would decrease blood pressure further. It's why it is contraindicated with nitroglycerin.

    It also enhances NOO signaling, one theory indicates peroxynitrite enhances symptoms of CFS.

    It's ability to increase oxygen intake due to this mechanism is interesting, and palliative actions may occur.

    There is limited risk to sildenafil if you want a trial run.
     
  10. ramakentesh

    ramakentesh Senior Member

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    While increased nitric oxide free radicals are implicated in CFS, actual research on the topic tends to suggest the opposite and in this theory CFS and primarily a form of POTS is caused by reduced nitric oxide biolavailability.
    So in theory, viagra by acting in cGMP to potentiate nitric oxide would induce vasodilation and restore circulatory function and cerebral blood flow.
    Not all forms of POTS/CFS result in reduced blood pressure - in many blood pressure is maintained or actually increased.
     
  11. perovyscus

    perovyscus

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    It did seem like I was discouraging. However, I do believe it's a no-brainer to try.
    I don't have POTS or proscribe to the NOO theory, so I'm speculating from too far away.
     
  12. SickOfSickness

    SickOfSickness Senior Member

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    Midodrine seems like the inferior one to me. I'm not very versed in these things, but midodrine is very short acting (2-3 hour half life I believe) and has plenty of side effects.
     

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