Failed Clinical Trial

[jeanb]

The PRECEPT (CEP1347) trial was run with great hope. This drug was found to be safe in humans (phase 1) and on rats and monkeys, it actually slowed or stopped the progression of PD. And the drug company was so confident the drug would work on hymans that it ran a phase 2/3 clinical trial with 800 people with early PD, who had not yet started any traditional PD meds.

After 2+ years, the trial failed spectacularly. After reviewing the interim results, scientists found that not only did the drug not work, the people on the placebo did better than the people receiving the drug. What a shock for all. :eek:

But after all that, scientists decided to start a follow-on trial for the 800 people in the original - PRECEPT - trial. The new trial is named "POSTCEP" And these 800 people will be followed through POSTCEP until the end of their lives (or until the funding money runs out...) As one study doctor told me, "these 800 people are like a "control group" for PWP and we can learn a lot by following them. We've never had such a large group to study before."

As part of PRECEPT, the trial participants had a SPECT brain scan every two years. Its goal was to prove that SPECT and beta-cit could be used as a diagnostic tool for PD. And since then a new SPECT scan trial was begun to follow the folks in POSTCEPT for four more years - this time to follow and document the progression of PD.

While here at Yale, I"ve chatted with others from the original PRECEPT trial. We were extremely sorry when the original trial failed. But we are all proud to be a part of the follow-on studies. Scientists will gain knowledge about the progression of PD.

[ZucchiniFlower]

Unfortunate news, but it's good the patients will be followed for so long.

Do you know what tracer they used for the Spect scans?

Thanks,

~Zucchini

[jeanb]

ZF-

Beta-CIT is the isotope they use (it's radioactive - less than a full body CAT scan and less than approved limits - and that's about the sum of my knowledge... :rolleyes: ) -- still in clinical trials. I have no idea when they plan to apply for FDA approval.

[paula_w]

Jean,

Is that the sum of your knowledge because you are working from memory? Are you satisfied with the Informed Consent?


Paula

[GregW1]

Thanks Jean, for the info and the effort.
greg

[Stitcher]

SPECT being discussed, as well as many very interesting controversialy topics...nice to see that the doc's a listening. Hope there will be lots of news daily during the Congress. Should we all charter a plane and go listen to what they have to say about US!!

The 1st World Congress on Controversies in Neurology
http://www.comtecmed.com/cony/Default.aspx
Berlin, Germany
September 6 - 9, 2007

http://www.comtecmed.com/CONY/Uploads/assets/cony%202nd%20ann.pdf
Session: Parkinsonian syndromes

Capsule: Movement disorders with Parkinsonian features have been diagnosed using different methods, using different criteria, but the basic question remains of the nosologic(3) entities underlying these neurodegenerative diseases.
SPECT imaging in the differential
diagnosis of Parkinsonian syndromes


The whole agenda on PD is great:

PARKINSON’S DISEASE (PD)

Session: Pathogenesis of PD
Capsule: In spite of much research, the pathogenesis of PD is still contested. Is there one cause that can be thought of as initiating the cascade?

PD is a mitochondrial(2)dysfunction disease
PD is due to synuclein dysfunction(4)
Is PD a ferrinopathy?(1)
Olfactory dysfunction(5) in early PD suggests that the disease is caused by
a toxin


Session: PD: Motor aspects
Capsule: How can we control the motor complications in PD?
DBS vs apomorphine infusions in complicated PD
Is DBS ready for early PD?
Spheramine–cell therapy for parkinson’s disease

Session: Early PD
Capsule: Continuous dopaminergic stimulation in early PD may best prevent the development of motor complications
Is continuous dopaminergic therapy
really important in the initial stages of PD?
L-Dopa + COMT inhibitors
Transdermal agonists
Are rasagiline and selegiline neuroprotective?
Is L-Dopa still allowed as initial therapy for PD?

Session: PD: non-motor aspects
Capsule: Non dopaminergic symptoms may be more relevant than DA-responsive motor
symptoms in PD

The treatment of depression in PD patients
Is dementia inevitable in PD?
Compulsive behaviour is the most significant adverse event due to dopaminergic
Daytime somnolence(6) in PD – How to avoid and how to treat?

Session: Parkinsonian syndromes
Capsule: Movement disorders with Parkinsonian features have been diagnosed using different methods, using different criteria, but the basic question remains of the nosologic entities underlying these neurodegenerative diseases.
SPECT imaging in the differential diagnosis of Parkinsonian syndromes

Debate: Are PSP and CBGD the same disease?


(1) Ferritin: The major iron storage protein. The blood level of ferritin serves as an indicator of the amount of iron stored in the body.

Ferritin has the shape of a hollow sphere that permits the entry of a variable amount of iron for storage (as ferric hydroxide phosphate complexes). Liver and spleen ferritin consists of 24 subunits of 2 kinds, the heavy and the light subunit. The genes that encode the light and heavy chains are on different chromosomes. The light chain genes are in chromosome region 19q13.3-q13.4 while those for the heavy chain are in chromosome region 11q12-q13.

Mutations in the ferritin light chain are responsible for a disease called the hyperferritinemia-cataract syndrome characterized by cataracts (opacities in the lens of the eye) and high levels of ferritin in the blood.
http://www.medterms.com/script/main/art.asp?articlekey=3410

(2) Mitochondrial myopathy: A group of neuromuscular diseases caused by damage to the mitochondria (http://www.medterms.com/script/main/art.asp?articlekey=4398), energy-producing structures in cells that serve as power plants. Nerve and muscle cells require a great deal of energy and are particularly impaired by mitochondrial dysfunction.

Some of the more common mitochondrial myopathies include the Kearns-Sayre syndrome (http://www.medterms.com/script/main/art.asp?articlekey=30811), myoclonic epilepsy with ragged-red fibers, and the MELAS syndrome (http://www.medicinenet.com/melas_syndrome/article.htm) of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes.

The onset of most mitochondrial myopathies is before the age of 20. They often begin with muscle weakness. During physical activity, muscles may become easily fatigued or weak. Muscle cramping is rare, but may occur.

Aside from muscle weakness and exercise intolerance, the symptoms of mitochondrial myopathy may include nausea, vomiting, headache, seizures, stroke-like episodes, and dementia; droopy eyelids, limited mobility of the eyes, blindness, and deafness; heart failure and heart rhythm disturbances (arrhythmias); and movement disorders.

There is no specific treatment for mitochondrial myopathy. However, physical therapy can extend the range of movement of muscles and improve dexterity. Vitamins such as riboflavin, coenzyme Q, and carnitine (an amino acid) may provide some subjective improvement in fatigue and energy levels in some patients.

The prognosis for these disorders ranges in severity from progressive weakness to death.
http://www.medterms.com/script/main/art.asp?articlekey=6374

(3) Nosology: The systematic classification of diseases, or the branch of medical science that deals thereto. The adjective is nosologic. There is "ongoing nosologic controversy and confusion" concerning "dementia with brainstem and neocortical Lewy bodies" (Neurology,1997;48:126).
http://www.medterms.com/script/main/art.asp?articlekey=23897

(4) Synuclein: A family of structurally related proteins that are prominently expressed in the central nervous system. See: Alpha-synuclein (http://www.medterms.com/script/main/art.asp?articlekey=25040).
http://www.medterms.com/script/main/art.asp?articlekey=25043

(5) Olfactory Dysfunction: http://www.medscape.com/viewarticle/417766_3

(6) Solnolence: Somnolence: Sleepiness, the state of feeling drowsy, ready to fall asleep. A person experiencing somnolence is somnolent and is acting somnolently.

Somnolence, somnolent, and somnolently go back to the Latin "somnus" meaning (please don't yawn) "sleep."
http://www.medterms.com/script/main/art.asp?articlekey=13097

[jeanb]

Thanks Carolyn -- yep we should all go. i've always wanted to go to Berlin. Wasn't able to when we lived in Germany during the Cold War.

jean :p