Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00425399 |
| Other study ID # |
lichtenbergCTIL2 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
January 22, 2007 |
| Last updated |
May 21, 2014 |
| Start date |
January 2007 |
| Est. completion date |
June 2008 |
Study information
| Verified date |
February 2009 |
| Source |
Herzog Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Israel: Ministry of Health |
| Study type |
Interventional
|
Clinical Trial Summary
In the current study we will study the effect of adding shiatsu treatment to conventional
therapy in work with hospitalized schizophrenic patients.
The hypotheses of this study are several:
1. Shiatsu can improve the patients' symptoms
2. Shiatsu can ameliorate neuromuscular side effects produced by standard anti-psychotic
treatment
3. Shiatsu can provide patients with tools to deal with the stresses of their illness
2. Methodology We propose an open pilot study in which a total of 20 patients of both sexes
will be enrolled. These patients will be drawn from the inpatient psychiatric wards at
Herzog Hospital.
Upon inclusion into the trial, all participants will receive shiatsu treatment, consisting
of two individual weekly 40-minute shiatsu treatment sessions for four weeks. Provider and
patient will be of the same gender. Standard pharmacotherapy will be provided as needed
during the treatment period. Medication and dosage will not be changed. If necessary,
benzodiazepines will be administered as required.
Outcome measures:
The following assessments will be included:
1. Medication: Use of SOS benzodiazepines
2. Clinical rating scales: PANSS, CGI, NOSIE, Hamilton Scales for depression and anxiety
1. Side effect scales: Simpson Angus Scale, AIMS scale, UKU scale 2. Neurophysiological
testing: Prepulse inhibition (PPI). 3. Neurocognitive testing: This will be performed using
the NIMH's Measurement and Treatment Research to Improve Cognition in Schizophrenia
(MATRICS) Consensus Cognitive Battery for Clinical Trials.
Description:
SHIATSU ADJUVANT THERAPY FOR SCHIZOPHRENIA Protocol for an Open Pilot Study
1. Background Schizophrenia is a severe, chronic mental illness that affects approximately
1% of the population worldwide. While the pharmacological treatments available have advanced
considerably in the last fifty years, there are limits to what they offer some patients,
especially in terms of improving dysphoria, sleep, mood, avolition, social functioning, and
anhedonia, which contribute greatly to the everyday misery of these patients.
Furthermore, some of the antipsychotic drugs induce side effects of parkinsonism,
akathisias, orofacial dyskinesias, dystonias, and their associated muscle pain, and
stiffness. The treatments used for those side effects are anticholinergic drugs (e.g.
trihexyphenidyl), benzodiazepines, and beta blockers. The number and variety of such drugs
suggests what clinicians know to be unfortunately true: there are no magic bullets for these
symptoms. These drugs are also not innocent, causing side effects of their own, contributing
to polypharmacy, and carrying a financial cost.
Schizophrenia, then, remains a debilitating illness whose treatment results are often
partial and may produce unpleasant side-effects. New approaches to supplement standard
modalities ought to be considered.
Shiatsu, or acupressure, is a holistic form of medicine originating in Japan but now widely
practiced throughout the world. Shiatsu involves applying pressure to "meridians" of the
body, much like acupuncture but without the needles. The shiatsu therapist views the whole
body as interconnected - stiffness in one part may reflect a problem in another, or
emotional disharmony. In accordance with the WHO definition of health as "a state of
complete physical, mental and social well-being and not merely the absence of disease or
infirmity," shiatsu massage aims to improve the overall well-being of its recipients by
manipulating the body.
Shiatsu theory is based on traditional Chinese medicine, which posits meridians of life
force (chi) running through the body, and aims to optimize health through manipulating the
body into maximal alignment. Disease, according to this approach, is as an accumulation of
damage and stress that causes the body to tense up in various areas, leading to health
disturbances. The treatment aims to loosen tense muscles and tendons and restore balance to
the body.
Shiatsu also involves a diagnostic process that is designed to locate sources of problems.
The main four areas of this process are the patient's appearance, his/her voice, the
specific complaints and medical history of the patient, and touch diagnosis. The touch is
meant to reveal areas of excess or lack of energy in the body or internal organs and
autonomic nervous system. Treatment is individualized according to the findings of this
examination.
Goals of treatment, in addition to releasing muscle and tendon tension and protecting these
structures, are to help the patient acquire an awareness of his or her body and psyche in
order to avoid recurrence of the problems, to identify life stressors (mental and physical),
and to strengthen the patient's overall energy flow and resilience to disease.
The two fields of shiatsu are do-in and anma. Do-in are the exercises that involve
stretching parts of the body combined with breathing exercises in order to loosen tense
joints and improve general circulation. Anma shiatsu is the more familiar massage-type
treatment. However, it is not performed for comfort or pleasure, as in Western massage, but
rather as a type of medical treatment. It is performed with a fully dressed patient, with
direct pressure applied with the practitioner's fingers. Both diagnosis and treatment are
performed this way, with the findings of the exam directing further actions.
How might the effects of shiatsu be explained in terms of Western medicine? In order to
answer this, we will consider research done not only for shiatsu but for acupuncture as
well, which has been more extensively examined. This is justified for two reasons: first of
all, shiatsu and acupuncture share the same understanding of human functioning and disease,
including the core concepts of chi and meridians, and accordingly they recognize the same
points along the body for applying pressure (shiatsu) or needles (acupuncture). Secondly, in
studies which have been conducted to test the effectiveness of alternative remedies,
acupressure and acupuncture have often been combined (e.g. Vachiramon & Wang, 2005; Melchart
et al, 2006).
2. Biological basis for shiatsu Medical research has attempted to understand how Chinese
medicine works its effects. Several theories have been developed which may be of relevance
to schizophrenia.
1. Endorphins: The most established effect of acupuncture is the release of endorphins,
which are endogenous opioid neuropeptides (Hökfelt, 1991; Sjölund et al, 1977).
Endorphin release appears to be closely related to the analgesic effects of
acupuncture. Endorphins also promote a general feel of well being and reduction of
tension which can have salutary effects in treating mental illness.
2. Cytokines: Cytokines mediate the inflammatory response. They also promote endorphin
release by the pituitary (Van der Meer et al, 1996). Drzyzga et al (2006) have reviewed
the possible connection between cytokines on the one hand, and neuropathological
changes, schizophrenia, and anti-psychotic medication mechanisms of action on the
other. A growing body of evidence suggests that cytokinins mediate neuropathological
changes in schizophrenia and the antipsychotic effects of medication. Acupuncture has
been shown to affect the cytokine system in animal (Liu et al, 2004) and human (Petti
et al, 2002) studies. The cytokine system is theoretically a pathway through which
acupuncture could produce therapeutic effects upon schizophrenia.
3. Glutamatergic mechanisms gained prominence as an important factor in the pathogenesis
and treatment of schizophrenia. In experiments with animals, N-methyl-D-aspartic acid
(NMDA) receptor antagonists have synergistically enhanced the anti-nociceptive effects
of electro-acupuncture (Zhang et al, 2002). Assessing the relationship between
glutamatergic activity and acupuncture effects could provide important information
about therapeutic mechanisms of action.
4. Neuropeptide Y (NPY): NPY's role in the CNS is not well understood. However,
appreciation for the possible role of NPY in the pathogenesis of severe mental disorder
has increased in recent years. NPY mRNA levels were significantly reduced in the
frontal cortex of patients with both schizophrenia and bipolar disorder (Kuromitsu et
al, 2001). NPY has also been shown to play a role in mediating the effects of
antipsychotic medication, in both animal (Huang et al, 2006) and human studies
(Obuchowicz et al, 2004). Interestingly, the effects of NPY may be mediated by
glutamatergic mechanisms (Rosse & Deutsch, 2004). This is relevant to our study because
NPY levels in saliva have been found to increase following acupuncture treatment
(Dawidson et al, 1998). This, then, is another possible mechanism through which
acupuncture can be clinically relevant to the treatment of schizophrenia.
Studies have already been carried out to assess the effectiveness of Chinese medicine in the
treatment of schizophrenia. In a recent review of five studies in the Cochrane Database
(Rathbone & Xia, 2005), acupuncture as adjuvant therapy provided with anti-psychotic
medication showed some evidence of improved outcomes on clinical rating scales and side
effect profiles, though overall the evidence was deemed insufficient to reach a definite
conclusion, and "more comprehensive and better designed studies" were recommended.
A second review (Moffet, 2006) of clinical trials of acupuncture for various medical
disorders made the important observation that too often, no meaningful physiological
rationale is provided for the proposed effectiveness of the treatment. Proposing a rationale
enables the investigator to suggest a testable causal hypothesis which can contribute to our
knowledge of the technique's mechanism of action.
In the current study we will focus on assessments of the glutamatergic system by
neurophysiological (prepulse inhibition) testing using prepulse inhibition (PPI). In this
paradigm, the subject is presented with an auditory stimulus, or "pre-pulse", which would
not ordinarily cause the subject to blink. Following this initial prepulse by a tenth of a
second comes a second, louder stimulus, the pulse, which would cause blinking were it not
preceded by the prepulse. Pre-pulse inhibition, a measure of sensory gating or filtering, is
determined by the reduction in blink response to a pulse following a pre-pulse as compared
to the blink response without the preparatory pre-pulse. Prepulse inhibition of the startle
response, which has been reliably demonstrated in both humans and animals (rev. in Braff et
al., 2001; Swerdlow et al., 2001), is a preattentive, automatic process.
Schizophrenia patients have been repeatedly shown reduced inhibition of the startle reflex
in PPI (rev. in Geyer et al., 2001). This loss of normal PPI is thought to be a measure of
the deficient sensorimotor gating (Braff and Geyer, 1990) that underlies sensory flooding
and cognitive fragmentation in these patients (McGhie and Chapman, 1961). Furthermore, some
studies report that PPI deficits may correlate with symptoms severity or cognitive and
functional impairment in schizophrenia and may partially or completely resolve with
antipsychotic drugs treatment (rev. in Braff et al., 2001).
One of the proposed models of PPI hypothesizes the involvement of glutamatergic, mainly
N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission. Glutamate is a key
inhibitory neurotransmitter. Glutamatergic neurotransmission may correlate with the
efficiency of sensory gating (Swerdlow and Geyer, 1999). Glutamatergic synapses have been
implicated in the regulation of PPI in rodents (Swerdlow et al., 2001).
In light of the possible connection between PPI and the glutamatergic system, we decided to
administer PPI to the subjects before and after the shiatsu treatment in order to assess
whether any ameliorating effect of shiatsu, which as noted can involve glutamatergic
mechanisms, may correlate with changes in the PPI.
We will also assess neurocognitive function using a battery of tests developed specifically
for use in assessing patients with schizophrenia.
3. Study goals: Based upon the rationales we suggested for utilizing shiatsu in the
treatment of schizophrenia, and based upon the studies which have already been performed, we
are proposing a pilot study to examine the efficacy of shiatsu as adjuvant therapy for
antipsychotics in the treatment of patients with schizophrenia.
The goals of this study are several:
1. To improve the patients' symptoms 2. To ameliorate neuromuscular side effects produced by
standard anti-psychotic treatment 3. To provide patients with tools to deal with the
stresses of their illness 4. To provide a basis for further investigation of the effects of
shiatsu 4. Methodology We propose an open pilot study in which a total of 20 patients will
be enrolled. These patients will be drawn from the inpatient psychiatric wards at Herzog
Hospital. They will be recruited by the treating physicians at these facilities. All
patients would be fully informed of the experimental treatments, goals, and possible
outcomes. Either the participant, or where relevant the court-appointed guardian, will be
required to provide informed consent. Participants will of course be free to discontinue
their participation for any reason at any time.
4.1 Inclusion Criteria:
1. DSM-IV-R diagnosis of schizophrenia or schizoaffective disorder
2. Ages 18 and over
3. Clinical status stable, as reflected by at least one month of drug treatment without
change of anti-psychotic drug or dosage.
4. Ability to cooperate with 40-minute sessions 4.2 Exclusion Criteria:
1. Active fracture or other orthopedic problem
2. Skin condition that renders treatment unsafe or painful
3. Active infection in skin or soft tissues, such as cellulitis
4. Any acute illness or other medical condition (e.g. solid tissue malignancy) for which
shiatsu may be contraindicated.
4.3 Study design Upon inclusion into the trial, all participants will receive shiatsu
treatment, consisting of two individual weekly 40-minute shiatsu treatment sessions for four
weeks. The shiatsu providers are all trained and certified by Tsabar College, an alternative
medicine training institute, and all have at least two years of post-training experience in
shiatsu. Each patient will receive all treatments from the same provider for the duration of
his or her treatment. Provider and patient will be of the same gender. The patient is
clothed with a shirt and full-length trousers or skirt during shiatsu. Treatment will not
include contact with sensitive regions of the body, such as the chest (in work with
females), pelvic, or inner thigh regions, or any other region of the body with which the
patient is not comfortable.
Standard pharmacotherapy will be provided as needed during the treatment period. Medication
and dosage will not be changed. If necessary, benzodiazepines will be administered as
required.
4.4 Rescue strategies and withdrawal from research In case of exacerbation, defined as an
increase of 2 points on the BPRS (or 4 to 6 on the individual items listed above), or of one
point on the CGI, the patient may receive clothiapine at a dose of up to 80 mg/day for not
more than 3 days within a 14-day period.
In case of relapse, defined as an increase of 3 points on the BPRS (or from 5 to 7 on
somatic concern, conceptual disorganization, hostility, suspiciousness, hallucinatory
behavior or unusual thought content), or of 2 points on the CGI, the patient will be
withdrawn from the study and appropriate treatment instituted. Furthermore, if the patient
deteriorates clinically in a way that may be related to treatment (e.g. paranoid fantasies
directed towards the shiatsu therapist), the research protocol for that individual will be
discontinued.
Significant emergent medical problems will also lead to the withdrawal of the patient from
the research.
4.5 Outcome measures
The following assessments will be included:
1. Medication
a. Use of SOS benzodiazepines: quantity and frequency
2. Clinical rating scales
1. PANSS
2. CGI
3. NOSIE
4. Hamilton Scales for depression and anxiety
2. Side effect scales:
1. Simpson Angus Scale
2. AIMS scale
3. UKU scale 3. Neurophysiological testing: Prepulse inhibition (PPI). This is performed
as follows: The eyeblink component of the acoustic startle reflex is measured using
electromyography of the obicularis oculi muscle. Two electrodes (6 mm) Ag/AgCl
electrodes filled with electrode gel (parker laboratories inc.) will be positioned
below and to the right of the patient's right eye, over the obicularis oculi muscle.
Electrodes will be placed to minimize potential electro-oculogram artifact.
Specifically, 1 electrode will be placed approximately 1 cm lateral to and 0.5 cm below
the lateral canthus, and the second electrode will be placed approximately 1.5 cm below
and slightly medial to the first electrode, conforming to the location of the
obicularis oculi fibers. A ground electrode will be placed behind the right ear over
the mastoid. All resistances will be less than 10 kOhm. Electrodes will be fixed to the
skin as close as possible to each other using adhesive collars. All acoustic stimuli
will be delivered binaurally through headphones (Maico, TDH-39-P). Subjects will be
seated comfortably in a softly lit after they will be informed of the procedure. The
prepulse and startle stimuli are bursts of white noise with a fixed interstimulus
intervals of 30, 60 and 120 ms for measuring PPI or 15 ms and 4500 ms for measuring
PPF. The startle session will begin with a 5-minute acclimation period of 70-dB white
noise, which will continue throughout the session, followed by six trial blocks. Block
1 consisted of six pulse-alone trials. Blocks 2 and 3 each consisted of 32 trials,
containing 8 pulse-alone and 24 prepulse-pulse trials presented in pseudorandom order.
Block 4 consisted of six pulse-alone trials. Block 5 consisted of six pulse-alone
trials and 12 prepulse-pulse trials and block 6 consisted six pulse alone trials. The
first, forth and sixth blocks will measure habituation as well as startle response, the
second and the third blocks will measure startle response and PPI and the fifth block
will measure PPF. The pulse alone stimulus is a 40 ms presentation of 115dB white
noise, the prepulse stimulus is a 20 ms (except the 15 ms interval stimulus which lasts
5 ms) presentation of 86 dB noise, both over 70 dB of continuous background noise.
Acoustic stimuli consist of pulse alone, prepulse and pulse, or no stimulus trials and
are presented in a fixed pseudorandom order. Electromyographic activity recorded by the
electrodes will be directed through a customized electromyographic amplifier to a
computerized startle response monitoring system for digitization and analysis (SR-LAB;
San Diego Instruments Inc, San Diego, Calif). The system will record 1000 one-ms
readings starting at the onset of the startle stimulus. Acoustic startle and prepulse
stimuli will be presented binaurally through headphones.
4. Neurocognitive testing: This will be performed using the NIMH's Measurement and
Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive
Battery for Clinical Trials. This recently-developed battery is recommended for use in
clinical trials of putative cognition-enhancing agents in schizophrenia. The MATRICS
battery, including Hebrew translations of relevant tests, is presently used in the
Stanley Foundation-sponsored Israel Multicenter D-Serine Trial (IMSER) (Dr.
Heresco-Levy - Co-Principal Investigator) and will be implemented by a trained
psychologist presently participating in this project.
5. Hypothesis: Shiatsu adjuvant therapy will improve psychiatric and motor symptoms in
patients after four weeks of therapy.
6.1 Potential Benefits: Shiatsu treatment is a pleasant experience involving applying
pressure manually to various points of the body. Furthermore, the research will itself
lead to more time spent by staff with patients, which is to the patient's benefit.
Beyond that we anticipate that shiatsu will be of benefit, alongside the standard
pharmacological treatment which will be continued, in enhancing the patient's wellbeing
and reducing medication side effects.
6.2 Potential Adverse Effects: Shiatsu is not known to carry any significant risks to
patients. It may rarely cause soreness, muscle cramps, or local pain. Patients will be
informed of this possibility and instructed to notify the shiatsu therapist if
discomfort occurs during treatment. Psychological distress may be aroused by the human
contact and touching that occurs during treatment. Patients will be advised about this
possibility as well. Patients wishing for any reason to discontinue the research will
of course be withdrawn from the study.
6.3 Significance of study: The treatment of schizophrenia could benefit from new
modalities to complement existing approaches. To date, no study has systemically
evaluated the use of shiatsu in treating schizophrenia, and only one study has
evaluated shiatsu in this population for drug induced myospasm. Due to the chronic
nature of this disease and the severe impairment of quality of life, any and all means
should be sought in combating the suffering inherent in this disease. Shiatsu may be a
cost-effective, pleasant, and well-tolerated treatment for some schizophrenia symptoms.
This study may pave the way for similar studies in other psychiatric patients.
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