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

Cort

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(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
 

Jody

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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.
 

Freddd

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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.

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 ...
 

Jody

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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 ...
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.
 

Freddd

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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.

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.
 

Jody

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Freddd,

I understand your reasoning.

Desperation can be a great motivator. Sometimes it even pays off. :)
 
C

cold_taste_of_tears

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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?
 

ramakentesh

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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.
 
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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.
 

ramakentesh

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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.
 
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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.
 

SickOfSickness

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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.