Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00315796 |
| Other study ID # |
J0387 |
| Secondary ID |
NCCAM: AT00437 |
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
April 17, 2006 |
| Last updated |
March 31, 2015 |
| Start date |
August 2004 |
| Est. completion date |
June 2005 |
Study information
| Verified date |
January 2005 |
| Source |
Johns Hopkins University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
Pain is a common and difficult problem for patients with cancer. It has been reported that
over 80% of cancer patients suffer from pain. Much of this pain is iatrogenic and related to
procedures. Dr. Grossman recently demonstrated that most patients undergoing bone marrow
biopsy have poor pain control during the procedure. Treatment of pain is almost entirely
with analgesic medications, principally opioids. These medications have numerous undesirable
effects such as sedation, confusion, hypotension and constipation that limit their efficacy
and utility. Drs. Diette, Lechtzin, Rubin and colleagues recently demonstrated that use of
nature sights and sounds (NSS), a simple, safe, and inexpensive intervention, decreases pain
during fiberoptic bronchoscopy, a procedure commonly performed to diagnose cancer and to
detect pulmonary complications of cancer therapy. Patients were randomly assigned to either
standard care with intravenous narcotics and benzodiazepines or standard care coupled with
view of a nature scene and use of nature sounds before, during, and after bronchoscopy. The
group assigned to the NSS reported significantly better pain control than the control group.
While these findings are novel and exciting, they raised several new questions that suggest
logical extensions of this work. It is not known whether this intervention can be applied to
patients in other settings, nor is it known whether comparison to standard care is an
appropriate control group. Further, the mechanism of action of NSS needs to be determined.
NSS may simply be a form of distraction therapy but it may have other properties. The theory
of biophilia proposes there are specific elements in nature imagery that exert beneficial
health effects. Because NSS appears to be a promising and safe intervention for the
treatment of pain, these investigators plan to perform a controlled clinical trial in cancer
patients undergoing invasive procedures. Patients will be randomly assigned to one of three
arms, standard care, NSS, and a non-nature based distraction technique. We will study the
efficacy of NSS for the management of procedure-related pain in oncology patients. The
findings will provide necessary background information to develop more definitive studies of
NSS that should be competitive for external funding. This exciting study will help develop a
harmless, inexpensive method to treat pain in cancer patients, that may complement or
replace analgesic medications.
Description:
Study Design: This is a randomized, controlled trial assessing the impact of nature sights
and sounds (NSS) on pain control in oncology outpatients undergoing bone marrow aspirate and
biopsy (BMBx) in the Weinberg Cancer Center at Johns Hopkins. One hundred twenty patients
will be assigned to one of three groups: 1) standard care, 2) NSS, 3) Music/Photo. The
primary outcome will be pain scores during the procedures as measured by the Hopkins Pain
Rating Instrument (HPRI). Patients in all groups will receive analgesic medications as
dictated by the personnel performing the procedure and the physicians responsible for their
clinical care. Patients in the NSS group will have Bedscapes nature scene murals placed at
the bedside in a location that is visible throughout the procedure. They will also listen to
a complementary audiotape during the procedure. The music/photo group will listen to city
sounds during the procedure and view a poster of a city skyline.
Setting: The study will be conducted in the Weinberg Cancer Pavilion of the Kimmel Cancer
Center at the Johns Hopkins Hospital.
Patient Selection: All patients 18 years and older with a diagnosis of cancer undergoing a
BMBx in the Johns Hopkins Oncology Center will be screened for enrollment in the study.
Informed Consent: The study design and consent procedure will be explained to all
prospective patients. If patients are interested in taking part in the study, written
informed consent will be obtained. The study nurse will administer a mental status exam and
assess eligibility. Consent and screening must occur within 5 days of the patient's
procedure.
Randomization: Blocked randomization will be used with variable block sizes to ensure
roughly equal numbers of patients in each study arm.
Study Interventions: All subjects will have pain managed by the physicians responsible for
their clinical care as dictated by those physicians. Subjects assigned to NSS will have
Bedscapes fabric panels depicting a scene of a mountain stream placed by the procedure table
at a location where it will be visible throughout the procedure. An accompanying audiotape
of complementary nature sounds will be played on portable tape players through headphones or
speakers. They will be instructed to listen to the tape and look at the nature scene as
frequently and for as long as they desire. The standard care group will have pain managed
according to current oncology center protocols but will not be allowed to use the
distraction interventions. The Music/Photo group will be played a tape of typical city
sounds and will have a poster of a city skyline placed by the procedure table. The city
skyline poster will be similar in size to the Bedscapes mural. The skyline image is a
daytime photograph without water, trees or other nature elements. The subjects will be asked
to listen to the music and view the picture during the procedure.
The HPRI will be used to measure pain. This is a plastic VAS with a sliding marker that
moves within a grove. The side facing the patient appears like a traditional VAS. It has a
10cm line with the anchors "No Pain" and "Worst Pain Imaginable". The opposite side of the
instrument is a 10 cm scale with markings every 0.5cm that enables the clinician to read and
record numerical values (see figure in appendix). Scores will be recorded to the nearest
0.5cm. All patients will have a baseline assessment of pain immediately prior to the
procedure. Subjects will be interviewed within one hour following the procedure and will be
asked to quantify their pain during the procedure.Patients will also complete a
questionnaire following the procedure in which they will score their level of pain control
during the procedure on a 5-point Likert scale, which was used in the bronchoscopy study .
Data Collection: Following the procedure patients will complete a set of questionnaires.
Questions will inquire about attitudes, beliefs and prior use of CAM. Patients in the NSS,
and Music/Photo groups will be asked whether they found the study intervention to be helpful
and if so what aspects of the intervention were beneficial. They will be asked to rate their
satisfaction with several aspects of the procedure including comfort, the nursing care, the
physician care, and the facility. Psychological distress will be measured with the Brief
Symptom Index 18 , negative mood states and anxiety will be measured with the Profile of
Mood States (POMS) . The BSI provides a global symptom severity score that will be used to
control for subjects' underlying psychological distress, while POMS is well suited to
measuring changes in mood related to the procedure. We will specifically focus on the
Tension-Anxiety, Depression-Dejection, Anger-Hostility, and Confusion-Bewilderment
subscales. Differences in response to pain will be measured with the Pain Catastrophizing
Scale . Salivary cortisol will be measured before and after the procedure as a
neuroendocrine marker of stress. Two baseline measurements of cortisol will be taken at
least 15 minutes apart prior to the procedure. Immediately following the procedure three
additional salivary cortisol samples will be collected approximately 15 minutes apart. The
study nurse will record heart rate, blood pressure and respiratory rate before and every 15
minutes during the procedures. The high and low systolic blood pressure, heart rate, and
respiratory rate will be extracted. The study nurse will record the percentage of time the
patient used the study intervention during the procedure. Patients will also be asked what
percentage of the time they used the intervention.
Outcomes: The primary outcomes is to determine if NSS is effective at reducing pain in
cancer patients undergoing invasive procedures, we will compare mean pain scores during the
procedure from the HPRI between the NSS group and the standard care group. We will also
compare the difference between ratings of baseline pain and pain during the procedure in the
two groups and the rating of pain control during the procedure between the groups. We will
also determine if NSS reduces pain more than non-nature based distraction therapy we will
compare pain ratings, and the difference in pain ratings from baseline to that during the
procedure between the NSS and the music/photo group. Lastly we will determine if NSS reduces
affective distress in cancer patients undergoing painful procedures we will compare mean
scores from the POMS between the three groups. Secondary outcomes that pertain to all
specific aims include vital signs during procedures and salivary cortisol levels. We will
also assess overall satisfaction with care, ratings of physicians, ratings of nurses, and
attitudes towards CAM interventions using Likert-type scales.
Sample Size: The primary outcome is difference in maximal pain level during procedures
between the NSS group and the Music/Photo group. Power estimates are based on the magnitude
of effect from the bronchoscopy study and the standard deviation of pain ratings in bone
marrow biopsies studied by Dr. Grossman. In order to have 80% power to detect a 2-point
difference in pain rating using the HPRI with an alpha error level of 0.05 we will need 29
patients in each group (total n=87). We plan to enroll 40 patients in each group (total
n=120) to compensate for study withdrawal and missing data. We will continue to enroll
patients until we have met these goals.
Data Entry and Management: The Biostatistics Core of the CAM center will provide
recommendations on data entry and analysis. Because this is a small, single center trial of
a relatively safe intervention there will not be a formal data safety monitoring committee.
However, Dr. Lechtzin will oversee data integrity.
Adverse Events Monitoring: This is a minimal risk intervention and we expect very few
adverse events. During our bronchoscopy study there was only one adverse event; a patient
became incontinent on the procedure table due to the sound of running water. Adverse events
to the experimental intervention will be assessed at the interview following the procedure
by recording all voluntary complaints of subjects and through structured interviews.
Attention will be directed to clinical adverse experiences associated with the procedure and
the experimental intervention. In addition, all study participants will be provided a
telephone number they can contact 24 hours/day, 7 days/week in case of questions, concerns,
or adverse events. Adverse events will be documented on a standardized case report form.
Summary reports of adverse events will be generated every three months. Dr. Lechtzin will
review these. All serious adverse events including death, hospitalization, and premature
withdrawal will be reported to the principal investigator within 24 hours of their
occurrence. The principal investigator will report all serious adverse events to the Johns
Hopkins IRB. Unexpected adverse events will be reported within 10 days.
Statistical Analysis: Analyses will be based on intention to treat. Analyses will be
performed comparing patients who used NSS to the standard care group and the Music/Photo
group. Descriptive analyses will be performed to assess subject characteristics
(demographics, disease characteristics, education, prior CAM use and attitudes). Procedure
characteristics will be compared including duration, complications, and medication usage.
Continuous variables will be represented as mean plus or minus SE, medians and interquartile
ranges. Bivariate analyses of outcomes will compare pain ratings, POMS subscales, and
psychological distress between the groups. Chi squared test or Fisher's Exact test will be
used to compare categorical variables such as age, gender, and race between groups. Unpaired
t-tests or the Kruskal Wallis test will be used to compare continuous outcomes such as Pain
Inventory scores. Pain scores will be analyzed as continuous variables and will also be
categorized into mild (0-2), moderate (3-6) and severe (7-10). Multivariate analyses will be
performed in order to adjust for possible confounding factors such as amount of narcotic
analgesics given and amount of local anesthetic used. Ordinal logistic regression models to
explain pain level by study intervention will be developed to adjust for factors such as
age, gender, race, procedure type, education level, local anesthetic dose, narcotic dose,
benzodiazepine dose, and BSI score. Additional factors will be included in the models if
they are significant in bivariate analyses. Logistic regression models will be developed to
determine factors associated with favorable response to NSS. Stepwise maximum-likelihood
ratio estimation with a significance level of 0.2 for removal and 0.1 for inclusion will
assist in model development. For all analyses significance will be set at p<0.05.
