Clinical Research Opportunities
There are currently many ongoing clinical trials and studies conducted at the Truong Neuroscience Institute (TNI).
When is the best time to start L-DOPA?
In one research effort, neurologists at TNI will start enrolling patients recently diagnosed with Parkinson's disease to examine the timing of starting L-DOPA (trade name Sinemet). There are long existing debates between scientists whether L-DOPA should be used in the early course of the disease or not. Many have raised concern about the possible damage that the early use of L-DOPA could result in if L-DOPA is found to have toxic effects on the brain because of the free radicals that it releases.
This study is the first large scale study of the relationship between the use of levodopa and the progression of the disease. It intends to determine whether L-DOPA should be initiated sooner or later after the diagnosis of Parkinson's disease has been made. It seeks to answer whether early use of Sinemet in Parkinson's disease is associated with a more rapid progression of the disease.
The study is carried out in 35 centers across the U.S. and is organized by the Parkinson's Study Group. Nationally 310 patients will be enrolled. The principal investigator at this site is Dr. Daniel Truong, a member of the Parkinson's Study Group. Patients will be seen by Dr. Truong only at the beginning and at the end of the study. During the mean time, they will be treated by Dr. Mayank Pathak, another neurologist at TNI for their parkinsonism.
Treatment of Parkinson's disease with medications such as Sinemet and Permax could sometimes result in unwanted side effects such as hallucination and odd thought content. Patients may see strangers living in their home, or even animals surrounding them. Odd thought contents such as believing that their spouse is trying to get rid of them may occur. Some patients retain insight, some do not.
These side effects are sometimes very bothersome to family members. The Truong Neuroscience Institute is investigating a marketed drug to control these side effects. However, we no longer enroll patients in this study.
There is evidence suggesting that motor fluctuations and dyskinesias are more related to the duration of levodopa therapy than disease progression. Dopamine agonists have received widespread clinical acceptance because of their potential to delay the initiation and reduce the amount of levodopa needed. Early Parkinson's disease patients could be managed successfully initially with agonist alone and later in combination with low dose levodopa. When compared to L-dopa monotherapy, patients treated with an agonist from the onset had a lower risk of developing dyskinesias. Agonists may therefore reduce the amount of free radical induced neuronal damage caused by the dopamine turn-over. There are also some evidences that dopamine agonists may confer neuroprotective benefit to Parkinson's patients.
Animal and clinical studies have shown that treatment of Parkinson's patient with long acting dopamine agonist should offer significant delay in the onset of complications and perhaps a slowing of the disease progression. It would be ideal, if the medication could be delivered steadily. None of the currently available dopamine agonists have an ideally stable 24 hours blood level. The "peak and trough" blood levels of multiple doses of dopamine agonists may result in non-physiological, pulsatile stimulus, which may contribute to the cause of the motor complications in Parkinson's disease. We are currently investigating the use of a transdermal patch to deliver dopamine agonist in a steady manner.
We also study apomorphine, a compound that has shown to be effective for late stage Parkinson's patients in studies conducted in Europe. This trial aimed at Parkinson's patients, who suffer marked fluctuation of the symptoms. Apomorphine has not been approved by the FDA and is currently still in the research phase.
Non-dopaminergic Drugs: Adenosine A2A Receptor Anatgonists
Until now, the focus of treatment of Parkinson's disease has been dopaminergic drugs such as levodopa (Sinemet), dopamine agonist and medications that block the destruction of levodopa. Recently non-dopaminergic drugs have been found to be effective in rodents and monkeys. This represent an exciting new approach for the treatment of Parkinson's disease as a new era of therapy may emerge.
It is known that adenosine receptor, namely adenosine A2A receptors, are abundant in the basal ganglia, especially in the striatum. They are predominantly localized on the neurons, which project to the globus pallidus internus (striatopallidal indirect pathway). This pathway is generally assumed to be hyperactive in PD. Adenosine A2A receptor anatgonists suppress this excessive activation. In animals certain A2A receptor anatgonists have prolonged the effect of either levodopa or apomorphine. We are currently investigating whether this compound improves dyskinesia and Parkinson's symptoms in PD patients as it is possible that blocking this excessive activation may be of therapeutic benefit.
Clinical Research Drug Studies
CYNAPSUS - CTH-300
NeuroDerm - ND0612
Other Ongoing Studies
We participate in a project named PROGENI. PROGENI is a multicenter research effort to examine family members of Parkinsonian disease patients, who have at least a sibling affected by Parkinson's disease. This study intends to help localize the gene for Parkinson's disease.
Other ongoing studies at the TNI including the investigation of Dysport (botulinum toxin A). Dysport is currently only available in Europe and slightly different from Botox, which is available in the US. We also provide Botulinum toxin B to certain patients with cervical dystonia.
In the near future, we will start a study investigating a precursor of levodopa for the treatment of Parkinson's disease patients with severe response fluctuations. This compound does not compete with amino acids. To facilitate a smooth absorption of Sinemet, some patients had to endure a protein free diet. Patients could avoid these requirements with this compound. We will initiate this study shortly.
Are you a student interested in research?
The Institute sometimes has research training positions available for students at high school and college levels. If you are interested in gaining experience in a research laboratory you may contact Gianni Truong at (714) 378-5635.
Positions are also available for graduate student and post-doctoral training in the areas of neuropharmacology, neurotoxicology and neuroscience. Those interested may contact Gianni Truong (714) 378-5635.