Preconditioning with Tefillin for Heart Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Jack Rubinstein
Must not be taking: Any medications
Disqualifiers: Active medical condition
No Placebo Group
Trial Summary
What is the purpose of this trial?A heart attack occurs when blood flow is disrupted to the heart and is related to both the blockage and flow restoration (reperfusion injury). An occlusion during a heart attack can be cleared (mostly via stents), but there are no methods to decrease reperfusion injury even though animal studies have found that "preconditioning" has powerful protective effects. Through the observation of Jewish men wearing tefillin the investigators have discovered a method of bringing preconditioning to patients at risk for heart attacks. This study will focus on women as the majority of people who wear tefillin (and have been studied) are men.
Will I have to stop taking my current medications?
Yes, you will need to stop taking your current medications to participate in this trial, as it excludes those who are currently using medication for any medical condition.
What evidence supports the effectiveness of the treatment Tefillin for heart disease?
Research on ischemic preconditioning, a process where brief episodes of reduced blood flow protect the heart from future damage, suggests that similar protective mechanisms could be beneficial in heart disease. While Tefillin is not directly studied, the concept of preconditioning has shown promise in reducing heart damage in various studies.
12345Is preconditioning with Tefillin safe for humans?
The research on ischemic preconditioning, which is a similar concept, suggests it is generally safe in humans, especially in the context of heart procedures. However, more studies are needed to fully understand its safety and effectiveness in different conditions.
14678How does the treatment Tefillin differ from other treatments for heart disease?
Tefillin is unique because it involves the nonocclusive wrapping of the arm, which may trigger a protective effect similar to remote ischemic preconditioning (RIPC). This method is different from traditional drug treatments as it uses a physical approach to potentially improve heart health by enhancing blood flow and reducing inflammation.
29101112Eligibility Criteria
This clinical trial is for women over the age of 18 who are not currently taking medication for any medical condition and do not have an active medical condition. It's designed to explore a potential heart protection method observed in Jewish men wearing tefillin.Inclusion Criteria
I am a woman older than 18.
Exclusion Criteria
I am currently taking medication for a health condition.
Active medical condition
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants wear tefillin in the traditional manner or apply capsaicin cream to the non-dominant arm
6 days
Daily visits for monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 weeks
Participant Groups
The study investigates whether using tefillin, which may induce 'preconditioning', can protect against heart damage during a heart attack. This concept comes from animal studies suggesting preconditioning reduces reperfusion injury when blood flow returns after being blocked.
2Treatment groups
Experimental Treatment
Active Control
Group I: TefillinExperimental Treatment1 Intervention
Wearing of tefillin in traditional manner
Group II: CapsaicinActive Control1 Intervention
Applying cream to non-dominant arm
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of CincinnatiCincinnati, OH
Loading ...
Who Is Running the Clinical Trial?
Jack RubinsteinLead Sponsor
References
Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. [2022]Therapeutic strategies to protect the ischemic myocardium have been studied extensively. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate lethal tissue injury, a process termed "reperfusion injury." Ischemia/reperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction. Ischemic preconditioning of myocardium is a well described adaptive response in which brief exposure to ischemia/reperfusion before sustained ischemia markedly enhances the ability of the heart to withstand a subsequent ischemic insult. Additionally, the application of brief repetitive episodes of ischemia/reperfusion at the immediate onset of reperfusion, which has been termed "postconditioning," reduces the extent of reperfusion injury. Ischemic pre- and postconditioning share some but not all parts of the proposed signal transduction cascade, including the activation of survival protein kinase pathways. Most experimental studies on cardioprotection have been undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of other disease processes. However, ischemic heart disease in humans is a complex disorder caused by or associated with known cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, insulin resistance, atherosclerosis, and heart failure; additionally, aging is an important modifying condition. In these diseases and aging, the pathological processes are associated with fundamental molecular alterations that can potentially affect the development of ischemia/reperfusion injury per se and responses to cardioprotective interventions. Among many other possible mechanisms, for example, in hyperlipidemia and diabetes, the pathological increase in reactive oxygen and nitrogen species and the use of the ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs and, in aging, the reduced expression of connexin-43 and signal transducer and activator of transcription 3 may disrupt major cytoprotective signaling pathways thereby significantly interfering with the cardioprotective effect of pre- and postconditioning. The aim of this review is to show the potential for developing cardioprotective drugs on the basis of endogenous cardioprotection by pre- and postconditioning (i.e., drug applied as trigger or to activate signaling pathways associated with endogenous cardioprotection) and to review the evidence that comorbidities and aging accompanying coronary disease modify responses to ischemia/reperfusion and the cardioprotection conferred by preconditioning and postconditioning. We emphasize the critical need for more detailed and mechanistic preclinical studies that examine car-dioprotection specifically in relation to complicating disease states. These are now essential to maximize the likelihood of successful development of rational approaches to therapeutic protection for the majority of patients with ischemic heart disease who are aged and/or have modifying comorbid conditions.
[How to use the paradigm of ischemic preconditioning to protect the heart?]. [2007]Ischemic preconditioning affords the most powerful protection to a heart submitted to a prolonged ischemia-reperfusion. During the past decade, a huge amount of work allowed to better understand the features of this protective effect as well as the molecular mechanisms. Ischemic preconditioning reduces infarct size and improves functional recovery; its effects on arrhythmias remain debated. Triggering of the protection involves cell surface receptors that activate pro-survival pathways including protein kinase C, PI3-kinase, possibly Akt and ERK1/2, whose downstream targets remain to be determined. Much attention has been recently focused on the role of mitochondrial K(+)ATP channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury. Based on these experimental studies attempts have been made to transfer preconditioning from bench to bedside. Human experimental models of ischemic preconditioning have been set up, including cardiac surgery, coronary angioplasty or treadmill exercise, to perform pathophysiological studies. Yet, protecting the heart of CAD (coronary artery disease) patients requires a pharmacological approach. The IONA trial has been an example of the clinical utility of preconditioning. It helped to demonstrate that chronic administration of nicorandil, a K(+)ATP opener that mimics ischemic preconditioning in experimental preparations, improves the cardiovascular prognosis in CAD patients. Recent experimental studies appear further encouraging. It appears that "postconditioning" the heart (i.e. performing brief episodes of ischemia-reperfusion at the time of reperfusion) is as protective as preconditioning. In other words, a therapeutic intervention performed as late as at the time of reflow can still significantly limit infarct size. Further work is needed to determine whether this may be transferred to the clinical practice.
Ischemic preconditioning: exploring the paradox. [2019]Brief transient episodes of nonlethal myocardial ischemia protect or "precondition" the heart and render the myocardium resistant to a subsequent more sustained ischemic insult. The hallmark of this phenomenon--documented in virtually all species and experimental models evaluated to date in countless laboratories worldwide--is the profound reduction in infarct size seen in preconditioned groups versus time-matched controls. Efforts to identify the cellular mechanisms responsible for this paradoxical ischemia-induced cardioprotection, to expand the definition of ischemic preconditioning beyond infarct size reduction, and, perhaps most importantly, to evaluate the efficacy of preconditioning in disease models and in the clinical setting, are all topics of intensive ongoing investigation.
Preconditioning by transient myocardial ischemia confers protection against ischemia-induced ventricular arrhythmias in variant angina. [2019]In experimental models, ischemic preconditioning of the heart protects against ischemic damage and ventricular arrhythmias during subsequent coronary occlusion. In this study, we investigated whether protection against ischemic suffering and ischemia-induced arrhythmias may occur after spontaneous transmural ischemia in humans.
Angina: who needs it? Cardioprotection in the preconditioning era. [2019]Over the past two decades, it has been demonstrated in various animal species that the myocardium possesses innate adaptive mechanisms that may render it more resistant to ischemic injury. Ischemic preconditioning, defined as the protection conferred to ischemic myocardium by prior episodes of brief sublethal ischemia, is one of the most potent of such adaptive phenomena. Extensive research over the past decade has alluded to the cellular mechanisms underlying this powerful means of reducing myocardial ischemia-reperfusion injury. Moreover, the possibility that such adaptive mechanisms might be inducible in the human heart has generated considerable excitement and enthusiastic research, which has significantly enhanced our understanding of the pathogenesis of ischemia-reperfusion injury. An insight into the mechanisms underlying the cardioprotective properties of ischemic preconditioning has, on the one hand, directed research aimed at identification of novel therapeutic agents for the treatment of ischemic heart disease, and on the other, questioned the use of potentially deleterious agents that may abolish the cardioprotective actions of ischemic preconditioning in patients with angina. Current studies are under way to evaluate the potential protection afforded by these "preconditioning" agents in patients with acute coronary syndromes, and some early reports provide some basis for optimism that a beneficial and clinically detectable improvement in myocardial protection may be possible. This article reviews our current knowledge of the cellular mechanisms responsible for mediation of ischemic preconditioning, the evidence for the existence of this phenomenon in humans, and its potential therapeutic applications.
Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart. [2018]The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.
Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats. [2022]To evaluate preventative effects of ischemic preconditioning (IP) in a rat model of intestinal injury induced by ischemia-reperfusion (IR).
Preconditioning the human myocardium: recent advances and aspirations for the development of a new means of cardioprotection in clinical practice. [2020]Ischemic preconditioning has been shown to be one of the most powerful means of protecting the myocardium from ischemic injury in experimental animal models, although the mechanism is incompletely understood. In this review we discuss the evidence for preconditioning occurring in ischemic syndromes in humans, whether the human myocardium can be preconditioned, and whether preconditioning would have a place as a therapeutic tool in clinical practice. Some studies evaluating patients after acute myocardial infarction have shown a better outcome in patients reporting angina before the onset of the infarction, but this is not a universal finding, and it is difficult to exclude other confounding factors, such as collateral flow, from influencing the results. More controlled prospective studies have evaluated patients undergoing percutaneous transluminal coronary angioplasty and have found less ST-segment change and less reported angina during the second balloon inflation when compared with the first. Again, it is impossible to completely exclude other causes for this effect, but the dependence on mechanisms that are known to be important for preconditioning in animal models does suggest the phenomena are the same. Further experiments using isolated human atrial muscle have shown that human myocardium can be preconditioned and that the mechanisms involved are similar to those elucidated in animal models (adenosine, protein kinase C, and ATP-dependent potassium channels). In clinical medicine preconditioning is most likely to benefit patients when it is used to protect against the ischemia induced by cardiac surgery. In this respect, a study has shown that in patients undergoing coronary artery bypass grafts, the reduction in ATP occurring during the first ischemic period is attenuated in those given an ischemic preconditioning protocol beforehand. Despite these advances, it is likely that the full potential of preconditioning in clinical practice will not be realized until the whole mechanism of protection is understood and a safe pharmacological "preconditioning" agent becomes available.
Tefillin use induces remote ischemic preconditioning pathways in healthy men. [2020]The present study assessed whether tefillin use (tight, nonocclusive, wrapping of the arm) elicits a remote ischemic preconditioning (RIPC)-like effect in subjects with both acute and chronic use. RIPC, created by short bursts of ischemia-reperfusion, has not been successfully taken to the bedside. Several large population studies have found that Orthodox Jewish men (who wear tefillin almost daily) have decreased cardiovascular mortality compared with non-Orthodox counterparts. We hypothesized that tefillin use is a relevant component in triggering a preconditioning effect. Jewish men ( n = 20) were enrolled; 9 men were daily tefillin users (conditioned) and 11 men were nonusers of tefillin as controls (naïve). Subjects were evaluated for adherence to traditional Jewish practice, had vital signs measured, blood drawn for analysis of circulating cytokines and monocyte function, and underwent brachial flow-mediated dilation to evaluate vascular reactivity at baseline (basal) and after 30 min of using tefillin (acute treatment). Under basal conditions, both groups had similar peak systolic velocity (SV), diameter, and flow volume, although the conditioned group had higher SV at 120 s postdeflation ( P = 0.05). Acute tefillin use augmented artery diameter and flow volume in both groups, with conditioned subjects experiencing higher SV than control subjects at 90 and 120 s postdeflation ( P = 0.03 and P = 0.02, respectively). Conditioned subjects had decreased inflammation, monocyte migration and adhesion, and endothelial activation compared with control subjects at baseline. Acute use of tefillin did not significantly alter monocyte function in either group. In this pilot study, acute tefillin use improves vascular function, whereas chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype. NEW & NOTEWORTHY We hypothesized that tefillin use among Orthodox Jewish men (who practice a nonocclusive leather banding of their nondominant arm) will induce a remote ischemic preconditioning phenotype. Chronic use of tefillin in Orthodox Jewish men was associated with increased systolic velocity and attenuated inflammation and monocyte chemotaxis and adhesion versus Jewish men who do not wear tefillin. Acute use of tefillin in both populations augmented brachial artery diameter and blood flow but not inflammatory profiles compared with baseline.
Tefillin use induces preconditioning associated changes in heart rate variability. [2023]Short bouts of occlusion of blood flow can induce a preconditioning response that reduces subsequent damage from longer periods of ischemia. It has been shown that ischemic preconditioning (IPC) can be elicited remotely (RIPC) through limitation of blood flow and as recently described via only pain sensation. Non-obstructive banding (NOB) through the donning of tefillin (a box with sacred texts attached to a leather strap that is traditionally bound to the non-dominant arm of Jewish adults during morning prayers) has been shown to elicit an RIPC response at least partially through pain sensation. This study evaluated the effects of NOB on heart rate variability (HRV) dependent factors that are known to be affected by various RIPC stimuli. We recruited 30 healthy subjects and subjected them to NOB versus control and found various HRV markers associated with RIPC to be changed in the NOB group. This finding provides further evidence that tefillin, likely through NOB induced RIPC changes, may still be a viable clinical pathway to prevent and decrease the morbidity associated with ischemic events.
Clinical effects of ischemic preconditioning. [2019]A variety of experimental studies have confirmed that preconditioning the myocardium by brief periods of ischemia represents a powerful cardioprotective effect resulting in a reduction of infarct size. After 15 years of research in the experimental laboratory, some evidence shows the existence of preconditioning in human patients with coronary artery disease: repeated balloon inflations before coronary angioplasty induce preconditioning-like effects; moreover, some studies demonstrate better clinical outcome in patients with angina before acute myocardial infarction, resembling a preconditioning effect. So far, a few drugs have been identified as potential mediators of preconditioning, e.g., adenosine, adenosine receptor agonists, and adenosine triphosphate-sensitive potassium channel openers. Before coronary angioplasty and heart surgery, these preconditioning mimetics might be used to protect myocardial tissue by means of preconditioning. Further research is required before preconditioning mimetics could be used for therapy in patients with chronic myocardial ischemia. Possible antipreconditioning effects of several drugs, e.g., sulfonylurea drugs have to be considered in the treatment of patients with coronary artery disease.
Ischaemic preconditioning and outcomes after angioplasty: effects of drug therapy. [2018]Ischaemic preconditioning is one of the mechanisms by which human myocardium and human life are protected from ischaemic insults. One of the clinical situations in which we can discuss preconditioning is repetitive coronary occlusions by balloon inflation during elective percutaneous transluminal coronary angioplasty (PTCA) for stable angina pectoris. The severity of myocardial ischaemia assessed by ST-segment elevation or chest pain is less during the second balloon inflation compared with the first, if the duration of the first coronary occlusion is sufficient to precondition the myocardium. Many drugs have been identified that produce a reduction or induction in indices of preconditioning during PTCA. Preconditioning-mimetic drugs include adenosine, bradykinin, nitroglycerin and nicorandil. It is of paramount importance that we investigate and develop preconditioning-mimetic drugs which may enable an increased tolerance to effort angina, limit infarction size in susceptible patients, and decrease the incidence of sudden cardiac death as a result of ventricular tachyarrhythmias.