Double-Blind, Placebo-Controlled Alcohol Study of Hythiam's Prometa Treatment Program Demonstrated Statistically Significant Improvement in Patients with Symptoms of Alcohol Withdrawal.
* Subjects exhibiting higher CIWA scores and who received the pharmacologic component of PROMETA achieved statistical significance in percent days abstinent when compared to those who received placebo.
* Subjects exhibiting higher CIWA scores showed significant improvement in other endpoints such as, time to first heavy drinking day, heavy drinks per drinking day, reduced cravings, and improved mood and sleep when compared to subjects with lesser symptoms of alcohol withdrawal.
* At baseline, subjects with higher symptoms of alcohol withdrawal showed statistical significance and greater severity on such measures as the alcohol dependence scale, the obsessive compulsive drinking scale, and drinks per drinking day, when compared to the same measures for subjects with lesser symptoms of alcohol withdrawal.
* The positive outcomes are consistent with prior literature that highlights the mechanism of action and the impact of pharmacologics on GABAA receptor function induced by ethanol withdrawal.1
* The data also provide clinical guidance as to the most appropriate therapeutic window during withdrawal to use the PROMETA Treatment Program on alcohol dependent patients.
These data are initial results and additional data reviews of the full 14-week study, including the results of functional MRI and acoustic startle (sound-based reflex test) are ongoing, and Dr. Anton plans to release these specifics in a peer-reviewed publication.
Dr. Anton's poster presentation at RSA offered the perspective that alcohol dependence treatments are few in number and not exceptionally effective, and that this is particularly true for an important subgroup of treatment seeking individuals who experience alcohol withdrawal. Importantly, the presentation concluded that PROMETA can reduce alcohol withdrawal symptoms, promote abstinence, reduce cravings, and improve mood and sleep in those who have symptoms of alcohol withdrawal.
Sixty subjects with alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV (DMS-IV), and with no other substance dependence or psychiatric disorders, were recruited into the study. The study design stratified subjects into 2 groups upon enrollment to the study, with a focus on comparing PROMETA to placebo for subjects with lower alcohol withdrawal, and also for subjects with higher alcohol withdrawal, as defined by their CIWA scores. All subjects received two days of infusions, and during the first two treatment days, each subject's alcohol withdrawal symptoms were assessed multiple times using CIWA scores. CIWA scores are based on a 67-point scale, and are a point-in-time assessment of withdrawal symptoms. The scores are typically used as a measure to guide the appropriate level of care and type of treatment. Subjects were classified as "Lower CIWA" if their baseline score was <7, and "Higher CIWA" if their scores were [greater than or equal to]7. In the Lower CIWA group (n=42), 25 subjects received the pharmacologic component of PROMETA compared to 17 for placebo, and in the Higher CIWA group (n=18), 8 subjects received the pharmacologic component of PROMETA compared to 10 for placebo. All subjects received six weekly sessions of standardized behavioral counseling, and were assessed at baseline and weekly for drinking, craving, mood, sleep and adverse effects from the treatment. The medications were well tolerated by all study subjects without significant adverse effects.
A typological study that performed a cluster analysis of subjects using the Alcohol Withdrawal Scale (AWS), which is based on a factor analysis of the CIWA scale, suggests that 40% to 60% of alcohol dependent patients presenting for treatment in that study may be exhibiting symptoms of withdrawal at a level appropriate for PROMETA.2 CIWA is a measure of a person's withdrawal severity at a point-in-time. Withdrawal symptoms typically commence within hours of drinking cessation and can last several days. During that time the severity of withdrawal symptoms, as measured by CIWA, can fluctuate through a cycle of increasing or decreasing severity and then a period of decline. The peak CIWA score in any given person is variable based on a number of factors including how frequently and how much an individual drinks prior to cessation. Therefore, the CIWA score of an individual presenting for treatment is a function of time from last drink, and the CIWA score may change over the course of a few hours.
Significantly for Catasys(TM), our managed care offering, which is aimed at the more costly patients who are high-utilizers of health plan services, this study may demonstrate the most impactful time to initiate treatment with the PROMETA Treatment Program. Effective treatment of alcohol dependent high-utilizers will help substantially reduce costs for third-party payors. As these patients are expected to be characterized by more severe states of substance dependence, it is likely that they will experience higher CIWA scores.
For the Lower CIWA group, PROMETA had no effect or a lesser response compared to placebo subjects, who fared better in the study. The mechanism of this finding is yet unclear. Further data analysis is ongoing for other study procedures, including functional MRI, among others.
Pre-clinical data supports that up-regulation of the GABA-A receptor alpha(4)-subunit occurs during withdrawal.1 Therefore, Lower CIWA subjects may represent a subgroup that had insufficient withdrawal symptoms at a point-in-time to realize the benefits of PROMETA. As previously noted, subjects were not required to maintain abstinence prior to the first treatment day, and this may have resulted in subjects presenting in the study with lower CIWA scores due to active drinking and higher blood alcohol levels during CIWA score tests. Further analysis is being conducted to determine how many subjects were drinking at baseline in the study and what impact this may have had on the outcomes.
This study was designed to provide all subjects with two infusions. However, subsequent to commencement of the study, a third infusion was included in the PROMETA Treatment Program provided in clinical settings. Based on reports from clinicians utilizing PROMETA, the added infusion day was intended to have the most appropriate impact on patients with lesser withdrawal symptoms on the first day of treatment, and who, due to continuous abstinence, might exhibit more significant withdrawal symptoms by day two or three and benefit from PROMETA.
Ongoing research includes two double-blind placebo-controlled studies utilizing three infusions: the first conducted by Joseph Volpicelli, M.D., Ph.D. on alcohol dependent subjects with lower CIWA scores, and the second by Jeffrey Wilkins, M.D. at Cedars-Sinai Medical Center that focuses on alcohol dependent subjects with higher CIWA scores. The results of these studies will further expand on the outcomes of this trial and the impact of PROMETA on alcohol dependent individuals in various states of withdrawal.
"We are very pleased with the results experienced by the Higher CIWA group in this study, as we are learning when to best use PROMETA during a patient's withdrawal process for the treatment of alcohol dependence," said Hythiam's Senior Vice President of Scientific Affairs, Dr. Gary Ingenito. "The impact of PROMETA on the Lower CIWA group remains unclear, and completion of the final analysis of all study data may provide more details on those outcomes. We also look forward to the completion of Dr. Volpicelli's study to provide additional data on the impact of PROMETA upon the treatment of alcohol dependence."
1. Biggio F., Gorini G., Caria S., Murru L., Sanna E. and Follesa P. Flumazenil selectively prevents the increase in alpha(4)-subunit gene expression and an associated change in GABA(A) receptor function induced by ethanol withdrawal. Journal of Neurochemistry. 2007;102(3):657-666.
2. Driessen M., Lange W., Junghanns K. and Wetterling T. Proposal of a comprehensive clinical typology of alcohol withdrawal - a cluster analysis approach. Alcohol & Alcoholism. 2005;40(4):308-313.
About the PROMETA([R] )Treatment Program
Hythiam's PROMETA Treatment Program is designed for use by health care providers seeking to treat individuals diagnosed with dependencies to alcohol, cocaine or methamphetamine, as well as combinations of these drugs. The PROMETA Treatment Program includes nutritional supplements, FDA-approved oral and IV medications used off-label and separately administered in a unique dosing algorithm, as well as psychosocial or other recovery-oriented therapy chosen by the patient and his or her treatment provider. As a result, PROMETA represents an innovative approach to managing alcohol, cocaine, or methamphetamine dependence that is designed to address physiological, nutritional, and psychosocial aspects of the disease, and is thereby intended to offer patients an opportunity to achieve sustained recovery. To learn more, please visit www.prometainfo.com.
Hythiam, Inc. provides through its Catasys(TM) offering, behavioral health management services to health plans, employers and unions through a network of licensed and company managed healthcare providers. Catasys offers integrated substance dependence solutions built around the patented PROMETA Treatment Program for alcoholism and stimulant dependence. The PROMETA Treatment Program, which integrates behavioral, nutritional, and medical components, is also available on a private-pay basis through licensed treatment providers and company managed treatment centers. Hythiam also researches, develops, licenses and commercializes innovative and proprietary physiological, nutritional, and behavioral treatment programs. Hythiam does not practice medicine or manufacture, distribute, or sell any medications and has no relationship with any manufacturers or distributors of medications used in the PROMETA Treatment Program. For further information, please visit www.hythiam.com.
Except for statements of historical fact, the matters discussed in this press release are forward looking and made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond the company's control that may cause actual results to differ materially from stated expectations. These risk factors include, among others, limited operating history and lack of statistically significant formal research studies, the risk that treatment protocols might not be effective, difficulty in developing, exploiting and protecting proprietary technologies, intense competition and substantial regulation in the healthcare industry; and additional risks factors as discussed in the reports filed by the company with the Securities and Exchange Commission, which are available on its website at http://www.sec.gov.
|Printer friendly Cite/link Email Feedback|
|Article Type:||Clinical report|
|Date:||Jul 8, 2008|
|Previous Article:||The Planet Unveils New Web Site.|
|Next Article:||MIVA Direct Names Mark A. Ribaudo VP, Direct Marketing.|