press release

Nov. 8, 2012, 7:00 a.m. EST

Pilot Study Extension Indicates Long-Term Treatment Durability with BioControl Medical's CardioFit(R) System

YEHUD, Israel & NEW HOPE, Minn., Nov 08, 2012 (BUSINESS WIRE) -- BioControl Medical has announced that pilot study extension results unveiled at the American Heart Association Scientific Sessions 2012 have indicated durability of treatment with its CardioFit(R) system for heart failure. Presented on November 7 in "Long-term Benefits of Vagal Nerve Stimulation Therapy in Heart Failure," the extended study data showed that the CardioFit's favorable clinical effects - as demonstrated by improved hemodynamics, quality of life and six-minute walk test - were maintained in patients beyond the study's original six- and 12-month evaluation points, up to 24 months.(1)

"These results are an encouraging validation of vagus nerve stimulation's potential as an effective long-term treatment for heart failure," said Dr. Srdjan Raspopovic, Clinical Center of Serbia, Belgrade, Serbia, a CardioFit pilot study investigator who presented the data at AHA 2012. "Larger controlled studies are currently underway to confirm these findings, and if they do, we believe that VNS will become an important new treatment alternative in the heart failure armamentarium."

Conducted in Italy, Germany, The Netherlands and Serbia, the original multi-center pilot clinical study of the CardioFit was designed to assess the six-month safety and clinical response to the therapy in 32 patients with NYHA II-IV heart failure on optimized background medical therapy.

Study data showed that patients experienced sustained significant improvement across key clinical measures at six and 12 months, including left ventricular function and structure, heart rate variability, and resting heart rate.(2) Patients also showed improvement in self-reported quality of life surveys and six-minute hall walk tests.(2) The study extension's 24-month data, available on 19 patients, showed sustained clinical improvement with the CardioFit therapy. Patient follow up now extends beyond four years, with good therapy tolerance and no reported safety issues.

"The extended pilot results are important data that build on BioControl Medical's growing body of research supporting VNS for the treatment of heart failure," said Ehud Cohen, Ph.D., chief executive officer of BioControl Medical. "We thank the investigators for their rigorous work assessing the long-term effects of CardioFit in our early study, and we look forward to gathering more data on a broader population of patients as our pivotal clinical trial continues to advance."

The safety and efficacy of the CardioFit is being explored further in the INOVATE-HF (INcrease Of VAgal TonE in Heart Failure) global, multi-center, investigational device exemption (IDE) clinical study. Initiated in April 2011, INOVATE-HF is a prospective, randomized, controlled clinical study that will evaluate the system's potential to reduce hospitalization and death among patients with HF, while also exploring whether combined treatment with CardioFit and prescription drug therapy is more effective than drug therapy alone.(3)

INOVATE-HF will ultimately enroll up to 650 patients at up to 80 centers in the United States and Europe. Results of the INOVATE-HF study will be used to support a Premarket Approval Application (PMA) to the U.S. Food and Drug Administration (FDA) for market clearance of CardioFit.

About the CardioFit

The CardioFit system consists of a stimulator, a sensor lead and a stimulation lead, which are implanted under the skin of the chest. The sensor lead is extended from the stimulator to the right ventricle of the heart, and the stimulation lead is extended from the stimulator to the vagus nerve on the right side of the neck. Once activated, the stimulator's electrical pulses are transferred via the stimulation lead to the vagus nerve. At the same time, the sensor lead monitors changes in heart activity and turns stimulation on or off accordingly. Like a pacemaker, the CardioFit System can be programmed on and off via external wireless communication with the device.

About BioControl Medical

Headquartered in Yehud, Israel with offices in New Hope, Minn., BioControl Medical develops and markets advanced implantable devices for the treatment of autonomic disorders, conditions whereby the autonomic nervous system ceases to function properly, resulting in a disruption to the control of involuntary body processes. The devices enable controlled electrical stimulation of various nerves to achieve therapeutic results. For more information on BioControl Medical, visit www.biocontrol-medical.com .

Caution: In the United States, the CardioFit is an investigational device. Limited by Federal (or United States) law to investigational use.

References
(1)Dennert R, et al. "Long-term Benefits of Vagal Nerve Stimulation Therapy in Heart Failure." American Heart Association Scientific Sessions 2012.
(2)De Ferrari GM, Crijns HJ, Borggrefe M, Milasinovic G, Smid J, Zabel M, Gavazzi A, Sanzo A, Dennert R, Kuschyk J, Raspopovic S, Klein H, Swedberg K, Schwartz PJ. "Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure." Eur Heart J (2011) 32 (7): 847-855.
(3)Hauptman PJ, Schwartz PJ, Gold MR, Borggrefe M, Van Veldhuisen DJ, Starling, RC, Mann DL. "Rationale and study design of the INcrease Of Vagal TonE in Heart Failure study: INOVATE-HF." American Heart Journal (June 2012) 163 (6): 955-962.
SOURCE: BioControl Medical

http://www.marketwatch.com/story/pilot-study-extension-indicates-long-term-treatment-durability-with-biocontrol-medicals-cardiofitr-system-2012-11-08

J Neural Transm. 2012 Nov 2. [Epub ahead of print]

Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study.

Hein E, Nowak M, Kiess O, Biermann T, Bayerlein K, Kornhuber J, Kraus T.

Source

Frankenalb-Klinik Engelthal, Clinic for Psychiatry, Psychotherapy, Psychosomatic Medicine, and Addiction Rehabilitation, Reschenbergstraße 20, 91238, Engelthal, Germany, ernst.hein@yahoo.de.

Abstract

Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes. Recently, a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed. In healthy subjects, a prominent fMRI BOLD signal deactivation in the limbic system was found. The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time. A total of 37 patients suffering from major depression were included in two randomized sham controlled add-on studies. Patients were stimulated five times a week on a daily basis for the duration of 2 weeks. On days 0 and 14, the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were assessed. In contrast to sham-treated patients, electrically stimulated persons showed a significantly better outcome in the BDI. Mean decrease in the active treatment group was 12.6 (SD 6.0) points compared to 4.4 (SD 9.9) points in the sham group. HAMD score did not change significantly in the two groups. An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study. Regarding the limitations of psychometric testing, the risk of unblinding for technical reasons, and the small sample size, further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields.

PMID:

23117749

[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23117749

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• BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation.[J Neural Transm. 2007]
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  Kraus T, Hösl K, Kiess O, Schanze A, Kornhuber J, Forster C. J Neural Transm. 2007; 114(11):1485-93. Epub 2007 Jun 14.
• Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis.[Ont Health Technol Assess Ser....]
  Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis.

  Health Quality Ontario. Ont Health Technol Assess Ser. 2004; 4(7):1-98. Epub 2004 Jun 1.
• Sensitivity to detect change and the correlation of clinical factors with the Hamilton Depression Rating Scale and the Beck Depression Inventory in depressed inpatients.[Psychiatry Res. 2012]
  Sensitivity to detect change and the correlation of clinical factors with the Hamilton Depression Rating Scale and the Beck Depression Inventory in depressed inpatients.

  Schneibel R, Brakemeier EL, Wilbertz G, Dykierek P, Zobel I, Schramm E. Psychiatry Res. 2012 Jun 30; 198(1):62-7. Epub 2012 Mar 22.
• Review Transcutaneous electrical nerve stimulation (TENS) for dementia.[Cochrane Database Syst Rev. 2003]
  Review Transcutaneous electrical nerve stimulation (TENS) for dementia.

  Cameron M, Lonergan E, Lee H. Cochrane Database Syst Rev. 2003; (3):CD004032.
• Review Effects of auricular acupuncture-like transcutaneous electric nerve stimulation on pain levels following wound care in patients with burns: a pilot study.[J Burn Care Rehabil. 1990]
  Review Effects of auricular acupuncture-like transcutaneous electric nerve stimulation on pain levels following wound care in patients with burns: a pilot study.

  Lewis SM, Clelland JA, Knowles CJ, Jackson JR, Dimick AR. J Burn Care Rehabil. 1990 Jul-Aug; 11(4):322-9.

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Epilepsy Curr. 2012 Sep;12(5):188-91. doi: 10.5698/1535-7511-12.5.188.

Neurostimulation-past, present, and beyond.

Ben-Menachem E.

Source

Institution of Clinical Neuroscience and Physiology, Sahlgrenska Academy, Göteborgs University, 413 45 Göteborg, Sweden, ebm@neuor.gu.se.

Abstract

Neurostimulation as a treatment for epilepsy has been around for almost 20 years in the form of vagus nerve stimulation. Newer types of neurostimulation are being developed and stand on the brink of approval for use. The two newest therapies, not yet approved in the United States, are deep brain stimulation and the Responsive Neurostimulator System . In fact, in Europe, approval has already been given for deep brain stimulation and newer forms of vagus nerve stimulation. Efficacy is similar between these therapies, and side effects are moderate, so what will be the future? The challenge will be to learn how to use these therapies correctly and offer the right treatment for the right patient.

PMID:

23118604

[PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/23118604

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• Neurostimulation for epilepsy.[Handb Clin Neurol. 2012]
  Neurostimulation for epilepsy.

  Vonck K, Herdt Vd, Sprengers M, Ben-Menachem E. Handb Clin Neurol. 2012; 108:955-70.
• [Newer treatment of epilepsy--brain pacemakers and transcranial magnetic stimulation].[Rinsho Shinkeigaku. 2005]
  [Newer treatment of epilepsy--brain pacemakers and transcranial magnetic stimulation].

  Akamatsu N. Rinsho Shinkeigaku. 2005 Nov; 45(11):928-30.
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  Review Neurostimulation therapies for treatment resistant depression: a focus on vagus nerve stimulation and deep brain stimulation.

  Rizvi SJ, Donovan M, Giacobbe P, Placenza F, Rotzinger S, Kennedy SH. Int Rev Psychiatry. 2011 Oct; 23(5):424-36.
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  Wu C, Sharan AD. Neuromodulation. 2012 Sep 4; . Epub 2012 Sep 4.

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Br J Neurosurg. 2012 Nov 1. [Epub ahead of print]

Long-term effectiveness and tolerability of vagal nerve stimulation in adults with intractable epilepsy: a retrospective analysis of 100 patients.

Ching J, Khan S, White P, Reed J, Ramnarine D, Sieradzan K, Sandeman D.

Source

Department of Neurosurgery, Institute of Neurosciences, Frenchay Hospital , Bristol , UK.

Abstract

Data for 100 vagal nerve stimulation (VNS) patients were collected and analysed retrospectively. The mean seizure reduction was 17.86% (n = 67) at 6 months, 26.21% (n = 63) at 1 year, 30.43% (n = 53) at 2 years, 48.10% (n = 40) at 3 years, 49.44% (n = 32) at 4 years, 50.52% (n = 35) at 5 years, 45.85% (n = 31) at 6 years, 62.68% (n = 25) at 8 years, 76.41% (n = 9) at 10 years, 82.90% (n = 4) at 12 years. Evidence of statistical significance for mean seizure reduction over time was strong with all p values less than 0.05 except at 12 years (p = 0.125) where the sample size was small (n = 4). Mean seizure reduction was 49.04% and 51 (51%) patients were considered responders, defined as a 50% or more reduction in seizure frequency. Twenty-one (21%) patients suffered surgical complications. Of these 15 patients were self-limiting and 6 patients were irreversible or required a device revision. Fifty patients (50%) suffered from side-effects, while vagal stimulation cycled on (VNS on) post-operatively. However, of these, only one patient suffered from intolerable side effects requiring the device to be switched off temporarily. This study demonstrates the long-term efficacy in seizure reduction with the use of VNS. Complication rates and tolerability did not deviate greatly from that previously reported, indicating that VNS is a safe and effective treatment for seizure reduction in intractable epilepsy.

PMID:

23113878

[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23113878

 

Common Antidepressants Too Risky During Pregnancy, Researchers Say

But another expert disagrees, saying all options must be open to women faced with this situation

October 31, 2012 RSS Feed Print

By Amanda Gardner
HealthDay Reporter

WEDNESDAY, Oct. 31 (HealthDay News) -- Women who take a popular class of antidepressants during pregnancy may be risking the health of their developing fetus, and the risk may outweigh any benefit to the mother, a new review of data suggests.

According to new research, use of selective serotonin reuptake inhibitors (SSRIs) -- which include Celexa, Paxil, Prozac and Zoloft -- while pregnant can increase the risk of miscarriage, preterm birth, pregnancy complications such as preeclampsia and neurobehavioral problems such as autism later in life.

"There is clear and concerning evidence of risk when pregnant women use these medications," said Dr. Adam Urato, senior author of a study appearing in the Oct. 31 online edition of Human Reproduction.

On the other hand, he said, there is no clear evidence that SSRI antidepressants actually benefit the mother in terms of alleviating mild-to-moderate depression.

Not everyone agreed with the researchers' conclusions, however. Dr. Beatriz Currier is associate professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine.

She said there is no blanket recommendation as to how best to treat depression during pregnancy and "every woman who presents to a clinician has to undergo a case-by-case analysis of the benefits and risks of antidepressant therapy."

Currier also said that there is "no conclusive data about an increased risk of miscarriage being associated with antidepressants." Nor is there any reason to conclude the rate of preeclampsia or birth defects is higher, she said, although there is some evidence that antidepressant use may be associated with low birth weight babies.

According to background information in the study, antidepressants are the most widely prescribed medications among adults aged 18 to 44. Up to 13 percent of pregnant women take an antidepressant. Many of these may be women undergoing treatment for infertility, a condition which is often accompanied by depression.

In 2010, up to almost 7,000 babies conceived by in vitro fertilization (IVF) may have been exposed to an antidepressant, the study authors said.

In their research, Urato and his team looked at the existing literature on women who had fertility problems and were also taking SSRIs. They say they found a number of concerns.

First of all, some studies suggest that SSRIs may actually undermine women's efforts to get pregnant, the researchers said. And for those who do get pregnant, the drugs may increase the risk for miscarriage as well as congenital problems in their children. The most striking association was for use of Paxil (paroxetine) during pregnancy and the risk for congenital heart defects, they said.
The study authors noted that, in 2005, the U.S. Food and Drug Administration requested that Paxil's maker, GlaxoSmithKline, change Paxil's pregnancy category from a "C" to a "D" rating, indicating that it poses a risk to the fetus.

The authors also pointed to a 2011 study from Kaiser Permanente Medical Care Program of Northern California that found a "twofold increased risk of autism spectrum disorders associated with maternal treatment with SSRI antidepressants during the pregnancy, with the strongest effect associated with treatment during the first trimester."

On the other hand, isn't untreated depression in a mother-to-be a hazard for both mother and fetus? According to Currier, sometimes SSRIs remain the best option for women facing this situation.
"Generally speaking, for women with very mild depression, the first course of treatment is that of cognitive behavioral therapy or other non-pharmacological [forms] of treatment," she said. "But in many cases, patients with moderate and severe depression will, in fact, require antidepressant therapy in order to treat their comorbid psychiatric illness, which cannot be ignored or dismissed," Currier added.

However, Urato said that an increasing number of studies are finding that SSRIs have little clinical benefit for mild-to-moderate depression when compared with a placebo (inactive) pill.
Other alternatives may exist for women who are battling depression, added study lead author Alice Domar, executive director of the Domar Center for Mind/Body Health at Boston IVF. The center is described on its Web page as focused on "enhancing the mind/body connection" through interventions such as "acupuncture, psychology, nutrition and restorative yoga."

According to Domar, cognitive behavioral therapy, in which patients learn how to direct their thinking and behavior to more constructive ends, probably has the most evidence behind it.
Exercise also has demonstrated efficacy, and yoga may have some benefit, she added.

"What I don't want to do is scare the heck out of women who are pregnant and have severe depression," Domar said. "I'm not suggesting that someone who is suicidal stop taking antidepressants cold turkey. You have to look at the individual risk-benefit ratio. In that case [suicidality], the risk of harm to her and her baby is far higher than the risk posed by an SSRI. For those with mild or moderate depression, the ratio shifts the other direction," she noted.

And, Urato added, "We're not saying women should not take SSRIs. The goal is to give them information so they can make the right decision for them."

More information
There's more about dealing with depression during a pregnancy at WomensHealth.gov.

http://health.usnews.com/health-news/news/articles/2012/10/31/common-antidepressants-too-risky-during-pregnancy-researchers-say