Clinical trial NCT02286960
Conditions: Dysphonia
Sponsor: NYU Langone Health
Start date: 2013-07-01; Completion date: 2018-12-01
Enrollment: 36 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Despite the considerable use of oral steroids in the regular management of benign vocal fold lesions there is little evidence base in the literature. This study will investigate the efficacy of oral steroids for the treatment of vocal fold lesions in a controlled manner. The specific aim of this study is to determine the effectiveness of of a short course of oral steroids prior to behavioral voice therapy in patients with benign, phonotraumatic vocal fold lesions. Enrolled subjects will be randomized using a random numbers table to either receive oral steroids or no steroids prior to the initiation of voice therapy. The therapist and individuals involved in the collection and analysis of data will be blinded as to whether the subject received drug. Prior to initiation of therapy subjects will be asked to return for an interval evaluation during which they undergo videostroboscopy and voice evaluation. Subjects will enter then the voice therapy phase . After an initial evaluation to determine the best mode of therapy they will receive a behavioral voice therapy course, which includes a range of behavioral modifications and motor learning techniques, along with lifestyle measures. In all these phases acoustic and aerodynamic measurements will be collected as well as audio-visual material from the videostroboscopic exams. The investigators hypothesize that oral steroids will lead to a reduction in lesion size, which will substantially aid in the delivery and incorporation of voice therapy techniques, contributing to the improvement of overall laryngeal biomechanics and providing an ideal starting point for behavioral voice therapy.

Detailed description:
The study will investigate the potential added advantage of the use of steroids in patients undergoing voice therapy. Enrolled subjects will be randomized using a random numbers table to either receive oral steroids or no steroids prior to the initiation of voice therapy. The therapist and individuals involved in the collection and analysis of data will be blinded as to whether the subject received drug. Prior to initiation of therapy subjects will be asked to return for an interval evaluation during which they undergo videostroboscopy and voice evaluation. Subjects will enter then the voice therapy phase . After an initial evaluation to determine the best mode of therapy they will receive a behavioral voice therapy course, which includes a range of behavioral modifications and motor learning techniques, along with lifestyle measures. In all these phases acoustic and aerodynamic measurements will be collected as well as audio-visual material from the videostroboscopic exams. The measurements that will be collected in all these phases are the Voice Handicap Index (VHI)-10 , the noise to harmonic ratio H/N, the fundamental frequency Fo, The transglottic airflow and subglottic pressure. The investigators hypothesize that oral steroids will lead to a reduction in lesion size, which will substantially aid in the delivery and incorporation of voice therapy techniques, contributing to the improvement of overall laryngeal biomechanics and providing an ideal starting point for behavioral voice therapy.

Arms: arm 1: Prednizone pills. 4 day course 2 x 20mg per day. arm 2: Lactose Pills. 4 day course 2 x 20mg per day.
Interventions: intervention 1: Steroid intervention 2: Lactose Pills
Intervention descriptions: intervention 1: A short 4 day course is administered to the first group of patients with voice disorders before the initiation of voice therapy. intervention 2: 4 day course 2 x 20mg per da

Protocol documents:
Prot_SAP_000.pdf: 
Official Title of the Study 
Investigation of the Role of Steroids in Enhancing Voice 
Therapy Outcomes 
NCT Number 
NCT02286960 
Study ID 
13-00096 
Version Date 
June 19, 2013 
 


S13-00096: Investigation of the Role of Steroids in Enhancing Voice Therapy Outcomes 
RESEARCH PROTOCOL (version 6.19.13) 
 
 
SPECIFIC AIMS 
 
The recently-published clinical practice guidelines (CPG) for hoarseness (1) pointed out several 
significant deficiencies in the laryngology literature. One of the more confounding statements in the 
document was related to the paucity of evidence for the use of steroids for the treatment of 
patients with complaints of hoarseness, regardless of etiology. Specifically, the document only 
suggests a role for steroids in the context of ‘allergic laryngitis’ in vocal performers. To address this 
comment, we recently surveyed the greater otolaryngology community in an attempt to describe current 
practice patterns with regard to the use of steroids for voice disorders (manuscript in revision). The 
results of this survey confirmed our hypothesis: steroid use is, in fact, quite common among 
otolaryngologists for a variety of diagnoses underlying voice complaints. Admittedly, these types of 
surveys are fraught with confounds, but frankly, this mismatch between the literature and clinical 
practice presents an opportunity to address this rather large research gap in the study of this 
very commonly used drug class, one that would benefit from comparative effectiveness 
research.  
 
Our anectdotal experience suggests that steroids are effective in improving voice in patients related to 
the presence of benign vocal fold lesions. Specifically, we commonly use steroids to reduce edema 
surrounding benign lesions yielding short-term improvement in vocal quality. We also noticed that some 
patients will have sustained improvement in voice in the long-term following a short course of oral 
steroids. We hypothesize that these outcomes may be due to a reduction of laryngeal inflammation and 
phonatory pressures required due to improved glottal closure as well as reduced vocal fold mass, 
thereby improving the overall laryngeal biomechanics and providing an ideal starting point for 
behavioral voice therapy.  
 
The current proposal seeks to prospectively and systematically address these phenomena. 
Typically, patients diagnosed with benign vocal fold lesions are referred for voice therapy for treatment 
of such lesions that are deemed to be non-surgical cases. Voice therapy has shown benefit for the 
treatment of a variety of such lesions.(2-10) For the current study, we propose to introduce oral steroids 
as a variable prior to the initiation of voice therapy. We hypothesize that subjects in the steroid 
treatment group will have an enhanced voice therapy experience as evidenced by more rapid 
improvement, the necessity for fewer voice therapy sessions, and a more global voice 
improvement when compared to the non-steroid treatment group.  
 
Specific Aim #1. To determine the effectiveness of a short course of oral steroids prior to the 
initiation of behavioral voice therapy in patients with benign, phonotraumatic vocal fold lesions.  
 
We hypothesize that a short course of oral steroids with resultant diminished vocal fold edema will 
increase the efficacy of voice therapy for patients with benign, phonotraumatic lesions. Specifically, we 
hypothesize that the improved inflammatory profile of the vocal folds will allow for contemporary voice 
therapy techniques to optimize vocal efficiency with an increased likelihood for long-term translation to 
everyday scenarios. To address this hypothesis, we seek to perform a prospective, randomized trial to 
compare objective, subjective, and patient-based outcome measures between two cohorts: patients 
with benign vocal fold lesions that are assigned to voice therapy that will receive oral steroids 
immediately prior to the initiation of voice therapy and those who receive no steroids prior to therapy. 
 
Data obtained under the auspices of this mechanism will not only address a significant deficiency in the 
clinical practice guidelines, but also alter the course of treatment for many patients, potentially yielding a 
paradigm for optimal patient care.   
 


(a) Significance 
 
Glucocorticoids were first used in the 1940’s to treat severe rheumatoid arthritis.(11) The discovery of 
this class of drugs irreversibly changed the treatment of inflammatory disorders and led to the award of 
a Nobel prize. Since the initial discovery, steroids have found their way into everyday clinical use for a 
variety of different disorders. In Otolaryngology, steroids are used in the treatment of facial nerve 
disorders, chronic sinusitis, and airway disorders, among others.(12-18) Although used commonly for 
the treatment of voice disorders (unpublished data, manuscript in revision), very little evidence exists for 
their use.  
 
The clinical practice guidelines (CPG) for hoarseness (1), cites that the only evidence for steroid 
efficacy in treating vocal fold disease was for allergic laryngitis and for rheumatologic disorders.(19-22) 
However, in reviewing the citations, it is evident that the “evidence” for use in allergic laryngitis is just 
expert opinion. Since the publication of the CPG, one publication has reviewed the use of oral steroids 
in the treatment of patients with vocal fold polyps. In the study, the authors noted that 70.6% patients 
treated with oral corticosteroids had either complete resolution or shrinkage of vocal fold polyps. 
However, the retrospective nature of the study and the lack of controls make it difficult to make any 
definitive conclusions with regards to the true effects of these drugs on vocal fold polyps.  
 
Intralesional steroids have been studied to a greater degree.(23-28) The rationale for their use is based 
on the high local concentration of drug at the site of injection. In a prospective, multicenter study, Woo, 
et. al. demonstrated improvement in almost 85% of benign vocal fold lesion cases (Reinke's edema, 
vocal polyp, nodule, and scarring). In a similar study, Hsu, et. al. found a 91% positive response rate 
with complete remission in 59% in vocal fold polyp cases treated with intralesional steroid injection.(24) 
In another prospective study, injected steroids were found to resolve or improve vocal fold nodules in 
93% of cases by 4 weeks after treatment.(25) These studies point to the fact that steroids do have 
a positive effect on vocal fold pathology, at least when delivered in high doses. 
 
In our practice and in those at other voice centers, steroids (oral and intralesional) have a wide 
application in a variety of vocal fold lesions. We have used these drugs orally for the acute treatment of 
inflammatory conditions of the vocal folds, such as viral laryngitis and vocal fold hemorrhage.  We have 
also used them in an oral form in various other circumstances, including perioperative management of 
benign vocal fold lesions and for acute and chronic treatment of benign vocal fold lesions. Anecdotally, 
we have seen value in the use of these drugs orally taken for these indications, though we cannot point 
to any significant literature base that supports their use. This is a critical research gap that needs to 
be addressed. 
 
(b) Innovation 
 
The current study is innovative, as it will be the first of its kind—one that will prospectively study the 
efficacy of oral steroids for the treatment of benign vocal fold lesions in a controlled manner. As 
mentioned above, this is of importance, as these drugs are being used routinely in practice without any 
evidence base in the literature. Such a study is long overdue. 
 
The current proposal employs a controlled, prospective, randomized, blinded study design. There are 
many confounding variables in the treatment of vocal fold lesions.  For those treated non-surgically, the 
patients are typically prescribed voice therapy, which includes a range of behavioral modifications and 
motor learning techniques, along with vocal hygiene measures and education. Since it would be 
unethical to withhold voice therapy for many of these patients, we chose instead to include it in the 
study design, as described below. 
 
The current proposal is also innovative in that it will collect several different outcome measures, 
including objective, subjective, and patient-based outcome measure. The study will allow for 
quantification of lesion size before and after oral steroid treatment, expert rating of stroboscopy, 


subjective rating of vocal quality, and patient rating of voice handicap (Voice Handicap Index-10 or VHI-
10 (see attached questionnaire)).   
 
In addition, the study will also investigate the potential added advantage of the use of steroids in 
patients undergoing voice therapy. We hypothesize that oral steroids will lead to a reduction in lesion 
size, which will substantially aid in the delivery and incorporation of voice therapy techniques, since the 
reduced lesion size will likely improve glottal closure and reduce vocal fold mass, thereby improving the 
overall laryngeal biomechanics and providing an ideal starting point for behavioral voice therapy. 
 
(c) Approach 
 
Subjects and Protocol 
 
The specific aim of this project is to determine the effectiveness of a short course of oral steroids prior 
to the initiation of behavioral voice therapy in patients with benign, phonotraumatic vocal fold lesions. 
As mentioned above, the study is designed to be prospective, randomized, and controlled. The study 
group will be recruited from our patient population. Our Center serves the population of the greater 
metropolitan New York area and has a high volume of patients that present with benign, 
phonotraumatic vocal fold lesions. Subjects that are non-surgical candidates that are assigned to 
receive voice therapy at our institution by a single voice therapist (Gherson) will be eligible for the study. 
Potential subjects will be identified by the PI or research staff and will be enrolled right after their clinical 
visit if they agree to the study protocol and do not meet the exclusion criteria (Figure 1). Recruitment 
will be done solely from the PI’s clinical practice. The PI (Amin), research coordinator (Achlatis) or the 
co-Investigators (Gherson, Branski) will be obtaining written consent after their clinical visit. Participants 
will be provided a copy of the completed consent form. Subjects are free not to participate in the study 
and their decision will not alter the quality of medical treatment that they will be receiving. 
 
At the time of enrollment, the study coordinator will open a pre-sealed envelope that will assign a 
subject to either receive oral steroids or placebo prior to the initiation of voice therapy. There will be 
twenty envelopes each that will read either “steroid” or “placebo”. Replacement envelopes will be added 
if/when subjects drop out from the study.  
 
According to their assignment, subjects will then be dispensed pills and counseled on proper dosing 
and potential side effects.  Subjects assigned to the “steroid” arm will be prescribed two 20 mg 
prednisone doses per day (40 mg total), taken together in the morning for four days.  This dose was 
chosen as it is the most common dose used in our practice and is within the lower part of the starting 
range recommended for this drug for the treatment of other inflammatory conditions of the airway, 
including asthma. A four-day treatment regimen has demonstrated efficacy in our experience, while 
reducing the risk of side effects. 
 
The therapist (Gherson), the scientist that will be conducting the evaluation (Branski) and other 
individuals involved in collection and analysis of data will be blinded as to whether the subject received 
drug. The prescribing physician (also the PI) will not be blinded, as this would interfere with routine 
clinical care of the subject. The research assistant (Achlatis) will also be non-blinded, as he will be in 
charge of the randomization and tracking process. Neither of these two individuals will be directly 
involved in providing or directing therapy, nor will be involved in collection or analysis of the data. 
 
Prior to the initiation of therapy, subjects will be asked to return for an “interval evaluation”, which is a 
research visit. During this evaluation, subjects will undergo videostroboscopy and voice evaluation by 
one of the co-investigators (Branski). Measures to be collected are described in the following section. 
Subjects will be reimbursed $75 for the time and expense involved in returning for this research 
evaluation, which is considered outside of routine clinical care. The charges for this visit will also be 
paid by the research account for the same reason. 
 


Subjects will then enter the voice therapy part of the protocol. They will receive an initial evaluation, 
which is part of routine clinical care. This evaluation will be used to determine the best mode of therapy 
to pursue. Subjects will receive the form of therapy that specifically meets their needs. The therapist will 
then keep records of the subject’s progress, including a timeline of progress. Subjects will be asked to 
maintain a regular schedule with the therapist, as this is ideal and will allow for better tracking of time to 
improvement. During therapy, subjects will be asked to fill out VHI-10 forms on a bi-weekly basis. These 
forms will be collected for study purposes. 
 
At the completion of therapy, subjects will follow-up with the treating physician (Amin) for a routine 
follow-up clinical visit. During this visit, routine videostroboscopy and voice evaluation by the co-
investigator (Branski) will take place.  The general experimental design is summarized in Figure 2. 
 
Dependent Variables and Data Collection (Figure 3) 
  
1. Voice Handicap Index (VHI)-10. The primary dependent variable is difference in VHI-10 scores 
from baseline (pre-treatment). The VHI-10 is a standardized and validated instrument that 
measures patient perception of their voice disorder.(29)  It is administered routinely as a 
component of clinical care at the NYU Voice Center. Completed forms are scanned into the 
patient’s electronic medical record for easy access and longitudinal comparison. For this study, 
VHI-10 data will be collected during the initial, interval, and final evaluations. 
2. Video-Perceptual Analysis. Videostroboscopic clips will be collected during clinical visits to the 
NYU Voice Center per normal protocol.  Briefly, following application (spray) of topical 
oxymetazoline and 4% lidocaine, a flexible endoscope will be passed through the nasal cavity 
and into the pharynx.  Subjects will be asked to perform a variety of vocal tasks, including 
sustained phonation, rapid phonation, sniffing, and counting.  Each exam will be recorded as is 
routine in our practice. There will be a total of three videos collected from each subjects (initial, 
interval, and final). The images/video obtained will be used for two separate analyses, as 
described below. For the expert analysis of the videostroboscopy, the clips will be edited in a 
manner that allows for de-identification and shortening of the clips to demonstrate the most 
salient parts of the video, including clear imaging of the pathology and at least 5 seconds of 
continuous mucosal wave. The edited clips will then be sent to 6 expert reviewers 
(otolaryngologists with a strong laryngology background) for review. The clips will be paired as 
follows: initial with interval and interval with final. The videos will be presented in random order, 
followed by a rating form. On the rating form, the reviewers will be asked to rate change in both 
mucosal wave and glottal closure on a relative 3-point scale (worse, same, better), as described 
in our previous work.(30) The reviewers will then be asked to return the rating forms, so the data 
can be collated. Twenty (20) percent of the samples will be repeated randomly for both the 
expert reviewer and lesion measurement analyses to assess intra-rater reliability.  Data will also 
be subjected to analysis of inter-rater agreement.  
 
The second analysis will be to measure lesion size. This method has been previously described 
by our group.(30) Briefly, still images of the glottis will be obtained from the video such that the 
vocal folds are captured in an open position (at least 40 degrees at the anterior commissure). 
Image J software (NIH) will then be used to outline the lesion and measure the length of the 
ipsilateral vocal fold (as shown in Figure 4). The ratio of these will be used as the adjusted size 
variable. Measurements will be done bilaterally when appropriate.  
3. Audio-perceptual Analysis. Auditory perceptual analysis will be performed based on the 
protocol recently developed as a component of the Consensus Auditory-Perceptual Evaluation of 
Voice (CAPE-V). Subjects are asked to repeat pre-determined sentences into a microphone. The 
stimulus sentences are collected as a component of routine clinical care at the NYU Voice 
Center and archived permanently via the Computerized Speech Laboratory (KayPentax, 
Montvale, NJ). These digitized files will then be culled, edited, and presented in random fashion 
to three expert listeners (speech pathologists with particular expertise in voice who are 
uninvolved in the current experiment). The standardized CAPE-V forms will be employed using 


the visual analog scale. Data will be collected via measurement of the hatch mark on the 100mm 
line for each variable. Twenty (20) percent of the samples will be repeated randomly to assess 
intra-rater reliability. Data will also be subjected to analysis inter-rater agreement as well as the 
overall change from pre-therapy to the two treatment arms.  
4. Aerodynamic Analysis of Voice. Aerodynamic analysis of voice will be employed to quantify 
vocal efficiency (i.e., acoustic output as a function of the pulmonary pressure required to sustain 
phonation). These measurements are collected as a component of routine patient care at the 
NYU Voice Center using the Phonatory Airflow System (KayPentax, Montvale, NJ). Essentially, 
patients are instructed on the appropriate positioning and placement of the mask to ensure no air 
leakage. Patients are then instructed to produce five productions of /pa/ at their most comfortable 
pitch and loudness at a rate of approximately 1.5 syllables per second. This protocol is followed 
at least twice to ensure compliance. The middle three productions will then be subjected to 
analyses, specifically the variables of average phonatory pressure and dB output will be 
obtained. This protocol has been described extensively in the literature.(31)  
 
Data Analysis. 
 
In general, data analysis will consist of comparisons of the above collected outcome variables 
measures from initial to interval evaluations and from interval to final evaluations.  Where applicable, we 
will also conduct comparisons between initial and final evaluations.  
 
Research Versus Non-Research Procedures. 
 
Subjects enrolled in the study will be asked to take either steroid or placebo as described above.  
Although oral steroids are used regularly in the management of benign vocal fold lesions, in this study 
we randomize the subjects that will receive steroids versus placebo.  This is therefore considered a 
specific research procedure. 
 
Subjects enrolled in the study will also undergo the data collection procedures described in the section 
above entitled “Dependent Variables and Data Collection” a total of three times.  The initial set of 
procedures will be performed on the initial visit as a part of the routine clinical care for which the subject 
is visiting the NYU Voice Center. Similarly, the final study visit is considered part of routine clinical care 
and the procedures performed will not be performed specifically for research purposes.  The 
procedures performed on the second or interval visit will be considered “research procedures”, since 
they are being performed outside of routine clinical care.  Subjects will be reimbursed for their time and 
expense in participating in the interval visit and their visit costs will be covered by the study account for 
this visit as described above. A specific explanation of the procedures that will occur during each visit is 
provided below (each visit has the same set of procedures): 
 
The patient will complete the Voice Handicap Index (VHI)-10 upon arrival to the clinic. An  
Audio-perceptual Analysis and an Aerodynamic Analysis of Voice will be performed in the voice lab the 
speech pathologist (Branski or Gherson). Finally, the patient will be brought to the examination room, 
where a history and physical examination will be performed, followed by videostroboscopy. 
 
Investigational Drug Use. 
 
As mentioned, subjects will be randomized to receive prednisone or placebo.  Prednisone is a drug 
product lawfully marketed in the U.S.  The investigation is not intended to be reported to the FDA as a 
well-controlled study in support of a new indication for use and is not intended to be used to support 
any other significant change in the labeling for the drug.  The investigation is not intended to support a 
significant change in the advertising for the product. The route, dose and indication of the medication 
will be as per FDA approval. The investigation is conducted in compliance with the requirements for IRB 
review set forth in 21 CFR Part 56 and with the requirements for informed consent set forth in 21 CFR 


Part 50.  The investigation is conducted in compliance with 21 CFR 312.7 (regarding promotion and 
charging for investigational drugs). 
 
Risks/Benefits of Research Procedures. 
 
The procedures involving some level of risk that will be involved in this study are listed in below, along 
with a description of the potential risks and benefits. 
 
Videolaryngoscopy – As mentioned above, this procedure involves the use of topical nasal sprays and 
passage of an endoscope.  The use of oxymetazoline and lidocaine nasal sprays involves a small risk 
of self-limited nasal bleeding and an extremely low risk of an allergic reaction.  The benefit of their use 
is that they minimize the discomfort of the endoscope.  The risks of the endoscope include minor nasal 
discomfort, self-limited nasal bleeding, and gagging.  Vasovagal reactions do occur, but are extremely 
rare.  There is no particular benefit to the use of the endoscope, except to help guide diagnosis and 
therapy clinically. 
 
Steroids – As mentioned above, half of the subjects in the study will receive oral prednisone (see 
attached product information).  There is an extremely low risk of an anaphylactic reaction to 
prednisone. Other potential risks of long-term use of steroids include the following: sodium retention, 
fluid retention, congestive heart failure in susceptible patients, potassium loss, hypokalemic alkalosis, 
hypertension, muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, tendon rupture, 
vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathologic fracture of 
long bones, peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, 
ulcerative esophagitis, impaired wound healing, thin fragile skin, petechiae, ecchymoses, facial 
erythema, increased sweating, may suppress reactions to skin tests, convulsions, increased intracranial 
pressure with papilledema, vertigo, headache, menstrual irregularities, development of cushingoid 
state, secondary adrenocortical and pituitary unresponsiveness, decreased carbohydrate tolerance, 
increased requirements for insulin or oral hypoglycemic agents in diabetics, posterior subcapsular 
cataracts, increased intraocular pressure, glaucoma, exophthalmos, and negative nitrogen balance due 
to protein catabolism.  The exclusion criteria, relative low dosage and short duration of the intake of 
prednisone that is used in this project will minimize possible risks. 
 
The potential benefit of taking prednisone includes possible improved outcome with reference to faster 
healing time of the benign vocal fold lesion. 
 
Provisions to Protect Privacy of Data and Confidentiality of Subjects. 
 
Subjects will be recruited after their initial clinical visit if they meet the inclusion criteria.  Subjects will be 
approached in the exam room immediately after completion of their visit and the study will be explained 
by the PI, research coordinator, or co-investigators confidentially. 
 
All written consent forms and other study-related documents will be kept in a single folder located in a 
locked cabinet within the NYU Voice Center. Digital files related to the project, including collected data 
and the randomization key will be kept on a password-protected computer of the research coordinator. 
The final data spreadsheet will be kept on a separate computer within the clinic, where only the 
personnel involved in this study will have access. The videos from the laryngoscopic exams will be also 
kept on a password-protected computer that is located in the examination room of the clinic.  
 
Sample Size and Statistical Considerations.  
 
The sample size was based on assumptions related to the primary dependent variable (ΔVHI). Based 
on a cursory review of our current outcomes, we assumed a ΔVHI of 10 (SD=7) for the placebo plus 
voice therapy group and a ΔVHI of 14 (SD=7) for the steroid plus voice therapy cohort. Using these 
assumptions with an alpha error level of 0.05 and a power of 80%, a sample size of 20 in each group 


was determined to be adequate to demonstrate a statistical difference between the groups. To ensure 
adequate enrollment, approximately 60 subjects will be screened, assuming a 33% screen failure rate. 
The proposed sample size is certainly feasible during the award period given the clinical caseload at the 
NYU Voice Center.  The breakdown of the population characteristics for the proposed study group is 
listed below and is based on the demographics of the PI’s practice. 
 
Total Planned Enrollment: 40 
TARGETED/PLANNED ENROLLMENT: Number of Subjects 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
5 
5 
10 
Not Hispanic or Latino 
15 
15 
30 
Ethnic Category Total of All Subjects* 
20 
20 
40 
Racial Categories 
 
American Indian/Alaska Native 
0 
0 
0 
Asian 
2 
2 
4 
Native Hawaiian or Other Pacific Islander  
0 
0 
0 
Black or African American  
4 
4 
8 
White 
14 
14 
34 
Racial Categories: Total of All Subjects*  
20 
20 
40 
 
Each data will be analyzed separately and presented descriptively as a mean and standard deviation. 
Furthermore, each variable will be subjected to independent two-tailed t-tests to determine statistically-
significant differences between the two experimental arms. Given the diversity of outcomes and the fact 
that they are largely independent, there does not appear to be the need to perform a Bonferroni 
adjustment to avoid Type I error. However, the data will be scrupulously analyzed and if evidence of 
Type I error is observed, such an adjustment will be made.   
 
Timeline. 
 
It is anticipated that the project will take approximately 12 months to complete.  We estimate that 
recruitment and treatment will take place in 11 months and that there will be a 1-month period of data 
analysis. 
 
Research Staff. 
 
The following are the research staff for this study and their roles: 
 
Milan Amin, MD, Director, NYU Voice Center, Associate Professor, Dept. of Otolaryngology – will 
perform videostroboscopy and he has expertise in the diagnosis and management of vocal pathology. 
 
Ryan Branski, PhD, Assistant Professor, Dept. of Otolaryngology – will collect voice recordings and 
aerodynamic measures and has expertise in voice evaluation and conducting voice research. 
 
Shirley Gherson, MA, CCC-SLP, Rusk Institute of Rehabilitation – will provide voice therapy.  She is a 
voice pathologist and specialist in the rehabilitaion of the injured voice. 
 
Efstratios Achlatis MD, NYU Voice Center – will be the study coordinator.  He is a research associate 
and has expertise in conducting voice related research. 
 
Facilities. 
 


The research will be conducted at the clinical offices of Dr. Amin (PI), located at 345 East 37th Street, 
Suite 306, New York, NY 10016 and at Rusk Rehabilitation Outpatients Services, ACC- 240E 38th 
street, 17th floor, New York, NY 10016. The offices have the necessary equipment, personnel, and 
computer hardware/software for conducting the study. 
 
Limitations. 
 
We acknowledge that there are certain limitations to this study. The study sample size is relatively 
small, although sample size calculations determine that we should be able to demonstrate a significant 
change if one exists, our results would certainly be more robust with a larger cohort.  In this regard, we 
are limited by budget constraints, since the study is relatively expensive to run. The other major 
limitation of the study is that we are not differentiating between lesion types.  We feel that this is quite 
difficult to do in reality, since vocal fold lesions, even within a type, are quite variable. Of course, we 
could theoretically conduct a post-hoc analysis of lesion type as a variable, but our cohort size is likely 
too small for this. 
 
Future Directions. 
 
In the future, we will need to address the limitations by opening up a multicenter, prospective trial of oral 
steroids for benign phonotraumatic vocal fold lesions.  In this larger trial, it will be possible to 
differentiate effects of steroids on different lesion types.  In addition, it may be possible to investigate 
dose and formulation effects of different steroids. 
 
This project is a small part of a larger research program examining the role of glucocorticoids for clinical 
use for laryngeal lesions.  In addition to studying the use of oral steroids, we will also study the effects 
of intralesional steroids for a variety of vocal fold lesions types, including vocal fold fibrosis, which 
remains a major clinical problem. 
 
 
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11. 
Lloyd M. Philip Showalter Hench, 1896–1965. Rheumatology. 2002;41(5):582-4. 
12. 
Riffat F, Jefferson N, Bari N, McGuinness J. Acute supraglottitis in adults. Ann Otol Rhinol Laryngol. 
2011;120(5):296-9. 
13. 
Lieberman DM, Jan TA, Ahmad SO, Most SP. Effects of corticosteroids on functional recovery and 
neuron survival after facial nerve injury in mice. Arch Facial Plast Surg. 2011;13(2):117-24. 
14. 
Rajapaksa S, Starr M. Croup - assessment and management. Aust Fam Physician. 2010;39(5):280-2. 
15. 
Greco A, Gallo A, Fusconi M, Marinelli C, Macri GF, de Vincentiis M. Bell's palsy and autoimmunity. 
Autoimmun Rev. 2012;12(2):323-8. 
16. 
Howard BE, Lal D. Oral Steroid Therapy in Chronic Rhinosinusitis with and without Nasal Polyposis. 
Curr Allergy Asthma Rep. 2012. 
17. 
Poetker DM, Jakubowski LA, Lal D, Hwang PH, Wright ED, Smith TL. Oral corticosteroids in the 
management of adult chronic rhinosinusitis with and without nasal polyps: an evidence-based 
review with recommendations. Int Forum Allergy Rhinol. 2012. 
18. 
Smith TL, Kern RC, Palmer JN, Schlosser RJ, Chandra RK, Chiu AG, et al. Medical therapy vs surgery 
for chronic rhinosinusitis: a prospective, multi-institutional study. Int Forum Allergy Rhinol. 
2011;1(4):235-41. 
19. 
Dean CM, Sataloff RT, Hawkshaw MJ, Pribikin E. Laryngeal sarcoidosis. J Voice. 2002;16(2):283-8. 
20. 
Jackson-Menaldi CA, Dzul AI, Holland RW. Allergies and vocal fold edema: a preliminary report. J 
Voice. 1999;13(1):113-22. 
21. 
Jackson-Menaldi CA, Dzul AI, Holland RW. Hidden respiratory allergies in voice users: treatment 
strategies. Logoped Phoniatr Vocol. 2002;27(2):74-9. 
22. 
Ozcan KM, Bahar S, Ozcan I, Pasaoglu L, Sennaroglu E, Karaaslan Y, et al. Laryngeal involvement in 
systemic lupus erythematosus: report of two cases. J Clin Rheumatol. 2007;13(5):278-9. 
23. 
Campagnolo AM, Tsuji DH, Sennes LU, Imamura R. Steroid injection in chronic inflammatory vocal 
fold disorders, literature review. Braz J Otorhinolaryngol. 2008;74(6):926-32. 
24. 
Hsu YB, Lan MC, Chang SY. Percutaneous corticosteroid injection for vocal fold polyp. Arch 
Otolaryngol Head Neck Surg. 2009;135(8):776-80. 
25. 
Lee SH, Yeo JO, Choi JI, Jin HJ, Kim JP, Woo SH, et al. Local steroid injection via the cricothyroid 
membrane in patients with a vocal nodule. Arch Otolaryngol Head Neck Surg. 2011;137(10):1011-6. 
26. 
Mortensen M. Laryngeal steroid injection for vocal fold scar. Curr Opin Otolaryngol Head Neck Surg. 
2010;18(6):487-91. 
27. 
Tateya I. Laryngeal steroid injection. Curr Opin Otolaryngol Head Neck Surg. 2009;17(6):424-6. 
28. 
Woo JH, Kim DY, Kim JW, Oh EA, Lee SW. Efficacy of percutaneous vocal fold injections for benign 
laryngeal lesions: Prospective multicenter study. Acta Otolaryngol. 2011;131(12):1326-32. 
29. 
Rosen CA, Lee AS, Osborne J, Zullo T, Murry T. Development and validation of the voice handicap 
index-10. Laryngoscope. 2004;114(9):1549-56. 
30. 
Sheu M, Sridharan S, Kuhn M, Wang S, Paul B, Venkatesan N, et al. Multi-institutional experience with 
the in-office potassium titanyl phosphate laser for laryngeal lesions. J Voice. 2012;26(6):806-10. 
31. 
Stepp CE, Heaton JT, Stadelman-Cohen TK, Braden MN, Jette ME, Hillman RE. Characteristics of 
phonatory function in singers and nonsingers with vocal fold nodules. J Voice. 2011;25(6):714-24. 
32. 
Paul BC, Chen S, Sridharan S, Fang Y, Amin MR, Branski RC. Diagnostic accuracy of history, 
laryngoscopy, and stroboscopy. Laryngoscope. 2013;123(1):215-9. 
33. 
Paul BC, Rafii B, Achlatis S, Amin MR, Branski RC. Morbidity and patient perception of flexible 
laryngoscopy. Ann Otol Rhinol Laryngol. 2012;121(11):708-13. 
34. 
Paul BC, Branski RC, Amin MR. Diagnosis and management of new-onset hoarseness: a survey of the 
American Broncho-Esophagological Association. Ann Otol Rhinol Laryngol. 2012;121(10):629-34. 
 
 


 
Figure 1 
Inclusion Criteria 
Exclusion Criteria 
Age 18-80  
Males and Females 
Use of any glucocorticoids (oral, inhaled, 
or intravenous) within 3 months of the 
initial evaluation 
Presence of phonotraumatic lesion 
deemed to be etiologic for the complaint 
of dysphonia 
Known allergy or hypersensitivity to oral 
steroids 
Voice therapy deemed to be the primary 
(or at least initial) treatment to address the 
dysphonia 
Active infection 
Willingness to be an active participant in 
voice therapy  
Diabetes Mellitus 
Prior history of radiation to the neck 
Recent myocardial infarction 
Recent gastrointestinal surgery with bowel 
anastamosis (3 months) 
Active peptic ulcer 
Pregnancy 
Severe depression or history of psycosis 
History of recent laryngeal surgery (within 
12 months) 
Figure 1. Inclusion and exclusion criteria for the proposed trial.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3 


Dependent Variable 
Brief Description 
VHI (primary dependent variable) 
The change in VHI-10 scores from pre-treatment to following 
treatment 
Video-Perceptual Analysis 
Analysis of stroboscopic parameters by expert raters as well as 
quantification of lesion size 
Audio-Perceptual Analysis 
The CAPE-V stimuli will be analyzed using a visual analog 
scale with expert listeners 
Aerodynamic Voice Analysis 
Collection of acoustic output (dB) and pulmonary pressure 
(cmH2O) during /pa/ 
Figure 3. Dependent variables to be analyzed in the current proposal.   
 
Figure 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
Name_____________________________________________                    Date______________________ 
 
 
 
 
 
 
 
 
 
 
I would rate my degree of talkativeness as the following: (circle response) 
     
     1 
     2 
     3 
     4 
     5 
     6 
     7 
Quiet                         
 Average                                    Extremely 
Listener                        
  Talker                                       Talkative 
 
 
VHI-10 Instructions:  These are statements that many people have used to describe their voices and the effects of their 
voices on their lives.  Circle the response that indicates how frequently you have the same experience. 
 
My voice makes it difficult for people to hear me. 
0        1        2        3        4 
People have difficulty understanding me in a noisy room. 0        1        2        3        4 
My voice difficulties restrict personal and social life. 
0        1        2        3        4 
I feel left out of conversations because of my voice.  
0        1        2        3        4 
My voice problem causes me to lose income.  
0        1        2        3        4 
I feel as though I have to strain to produce voice. 
0        1        2        3        4 
The clarity of my voice is unpredictable. 
0        1        2        3        4 
My voice problem upsets me. 
0        1        2        3        4 
My voice makes me feel handicapped.  
0        1        2        3        4 
People ask “What’s wrong with your voice?” 
0        1        2        3        4 
 
 
Please check that you have answered all the questions. 
 
 
RSI Instructions:  These are statements that many people have used to describe their voices and the effects of their 
voices on their lives. Circle the response that indicates how frequently you have the same experience.  
 
Within the last MONTH, how did the following  
problems affect you? 
 
Hoarseness or a problem with your voice 
 
  0        1        2        3        4        5 
Clearing your throat 
 
 
 
 
  0        1        2        3        4        5 
Excess throat mucous  
 
 
 
  0        1        2        3        4        5 
Difficulty swallowing food, liquids or pills  
 
  0        1        2        3        4        5 
Coughing after eating or after lying down 
 
  0        1        2        3        4        5 
Breathing difficulties or choking episodes 
 
  0        1        2        3        4        5 
Troublesome or annoying cough 
 
 
  0        1        2        3        4        5 
Sensations of something sticking in your throat or a 
lump in your throat 
 
 
 
 
  0        1        2        3        4        5 
Heartburn, chest pain, indigestion, or stomach acid 
 
coming up 
 
 
 
 
 
  0        1        2        3        4        5 
 
 
Please check that you have answered all the questions. 
FOR STAFF USE 
1-  TALK 
____ 
2-  VHI-10 
____ 
3-  RSI 
____ 
4-  SVHI-10  
____ 
0 = No problem . . . .          . . . 5 = Severe problem  
0 = Never 
1 = Almost never 
2 = Sometimes 
3 = Almost always 
4 = Always 
IF YOU ARE A SINGER, PLEASE COMPLETE THE BACK OF THE PAGE. 


Singers Only: 
 
I sing the following kind of music      country         classical         choral           pop    
    rock        
(circle all that apply)    
 
    gospel          jazz 
     
other _________________ 
 
Singing is (circle one)     
primary source of income      secondary source of income     
   not source of income 
  
How would you categorize        
   professional entertainment          teacher/instructor          
your singing ? (circle)                        music/singing student                 amateur choir/singing group 
   
 
Singing Voice Handicap Index-10 
  
These are statements that many people have used to describe their singing and the effects of  
their singing on their lives. Circle the response that indicates how frequently you have the same  
experience in the last 4 weeks.  
 
 
  
Never 
Almost Never     Sometimes 
Almost Always     Always 
 
1) It takes a lot of effort to sing. 
0 
 1 
2 
3 
4 
  
2) I am unsure of what will come 
0 
 1 
2 
3 
4 
out when I sing. 
  
3) My voice “gives out” on me  
0 
 1 
2 
3 
4 
while I am singing. 
  
4) My singing voice upsets me.         0 
 1 
2 
3 
4 
 
 5) I have no confidence in my           0 
 1 
2 
3 
4 
singing voice. 
  
6) I have trouble making my               0 
 1 
2 
3 
4 
voice do what I want it to. 
  
7) I have to “push it” to produce        0 
 1 
2 
3 
4 
my voice when singing.                                                                                                
  
8) My singing voice tires easily.        0 
 1 
2 
3 
4 
   
9) I feel something is missing            0 
 1 
2 
3 
4 
in my life because of my inability 
to sing. 
  
10) I am unable to use my “high        0 
1 
2 
3 
4 
voice.” 
 
 


 
DELTASONE - prednisone   tablet 
Pharmacia and Upjohn and Company 
 
DESCRIPTION 
DELTASONE Tablets contain prednisone which is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally 
occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Prednisone is a white to practically white, odorless, 
crystalline powder. It is very slightly soluble in water; slightly soluble in alcohol, in chloroform, in dioxane, and in methanol. 
The chemical name for prednisone is pregna-1,4-diene-3,11,20-trione, 17,21-dihydroxy- and its molecular weight is 358.43. 
The structural formula is represented below: 
DELTASONE Tablets are available in 5 strengths: 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg. Inactive ingredients: 2.5 mg—Calcium 
Stearate, Corn Starch, Erythrosine Sodium, Lactose, Mineral Oil, Sorbic Acid and Sucrose. 5 mg—Calcium Stearate, Corn Starch, 
Lactose, Mineral Oil, Sorbic Acid and Sucrose. 10 mg—Calcium Stearate, Corn Starch, Lactose, Sorbic Acid and Sucrose. 20 mg— 
Calcium Stearate, Corn Starch, FD&C Yellow No. 6, Lactose, Sorbic Acid and Sucrose. 50 mg—Corn Starch, Lactose, Magnesium 
Stearate, Sorbic Acid, Sucrose, and Talc. 
 
ACTIONS 
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement 
therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in 
disorders of many organ systems. 
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli. 
 
INDICATIONS 
DELTASONE Tablets are indicated in the following conditions: 
1.  Endocrine Disorders 
Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be 
used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular 
importance) 
Congenital adrenal hyperplasia 
Hypercalcemia associated with cancer 
Nonsuppurative thyroiditis 
 
2.  Rheumatic Disorders 
As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: 
Psoriatic arthritis 
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy) 
Ankylosing spondylitis 
Acute and subacute bursitis 
Acute nonspecific tenosynovitis 
Acute gouty arthritis 
Post-traumatic osteoarthritis 
Synovitis of osteoarthritis 
Epicondylitis 
3.  Collagen Diseases 
During an exacerbation or as maintenance therapy in selected cases of: 
Systemic lupus erythematosus 
Systemic dermatomyositis (polymyositis) 
Acute rheumatic carditis 
 
4.  Dermatologic Diseases 
Pemphigus 
Bullous dermatitis herpetiformis 
Severe erythema multiforme (Stevens-Johnson syndrome) 
Exfoliative dermatitis 
Mycosis fungoides 
      Severe psoriasis 
 Severe seborrheic dermatitis 
 
 
 
 
 
 


 
5.  Allergic States 
Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment: 
Seasonal or perennial allergic rhinitis 
Bronchial asthma 
Contact dermatitis 
Atopic dermatitis 
Serum sickness 
Drug hypersensitivity reactions 
 
6.  Ophthalmic Diseases 
Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: 
Allergic corneal marginal ulcers 
Herpes zoster ophthalmicus 
Anterior segment inflammation 
Diffuse posterior uveitis and choroiditis 
Sympathetic ophthalmia 
Allergic conjunctivitis 
Keratitis 
Chorioretinitis 
Optic neuritis 
Iritis and iridocyclitis 
 
7.  Respiratory Diseases 
Symptomatic sarcoidosis 
Loeffler's syndrome not manageable by other means 
Berylliosis 
Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy 
Aspiration pneumonitis 
 
8.  Hematologic Disorders 
Idiopathic thrombocytopenic purpura in adults 
Secondary thrombocytopenia in adults 
Acquired (autoimmune) hemolytic anemia 
Erythroblastopenia (RBC anemia) 
Congenital (erythroid) hypoplastic anemia 
 
9.  Neoplastic Diseases 
For palliative management of: 
Leukemias and lymphomas in adults 
Acute leukemia of childhood 
 
10. Edematous States 
To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to 
lupus erythematosus 
 
11. Gastrointestinal Diseases 
To tide the patient over a critical period of the disease in: 
Ulcerative colitis 
Regional enteritis 
 
12. Nervous System 
Acute exacerbations of multiple sclerosis 
 
13. Miscellaneous 
Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous 
chemotherapy 
Trichinosis with neurologic or myocardial involvement 
 
 
 
 
 
 


 
CONTRAINDICATIONS 
Systemic fungal infections and known hypersensitivity to components. 
 
WARNINGS 
In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and 
after the stressful situation is indicated. 
Corticosteroids may mask some signs of infection, and new infections may appear during their use. Infections with any pathogen 
including viral, bacterial, fungal, protozoan or helminthic infections, in any location of the body, may be associated with the use of 
corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or 
neutrophil function.1 
These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence 
of infectious complications increases.2 There may be decreased resistance and inability to localize infection when corticosteroids are 
used. 
Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and 
may enhance the establishment of secondary ocular infections due to fungi or viruses. 
 
Usage in pregnancy 
Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing 
mothers or women of child-bearing potential requires that the possible benefits of the drug be weighed against the potential hazards 
to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy, 
should be carefully observed for signs of hypoadrenalism. 
Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased 
excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary 
salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. 
Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. 
Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, 
the response to such vaccines may be diminished. Indicated immunization procedures may be undertaken in patients receiving 
nonimmunosuppressive doses of corticosteroids. 
The use of DELTASONE Tablets in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis 
in which the corticosteroid is used for the management of the disease in conjunction with an appropriate anti-tuberculous regimen. 
If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as 
reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. 
Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chicken 
pox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. 
In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route 
and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution 
of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis 
with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular 
immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If 
chicken pox develops, treatment with antiviral agents may be considered. Similarly, corticosteroids should be used with great care in 
patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression 
may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe 
enterocolitis and potentially fatal gram-negative septicemia. 
PRECAUTIONS 
General Precautions 
Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative 
insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, 
hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be 
administered concurrently. 
There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis. 
Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. 
The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is 
possible, the reduction should be gradual. 
Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality 
changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be 
aggravated by corticosteroids. 
 
 
 
 


 
Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or 
other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer; renal insufficiency; hypertension; 
osteoporosis; and myasthenia gravis. 
Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. 
Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result 
in clinical remission. 
Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations 
of multiple sclerosis, they do not show that corticosteroids affect the ultimate outcome or natural history of the disease. The 
studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND 
ADMINISTRATION.) 
Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/ 
benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent 
therapy should be used. 
Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Since concurrent use of these agents 
results in a mutual inhibition of metabolism, it is possible that adverse events associated with the individual use of either drug may be 
more apt to occur. 
 
Drug Interactions 
The pharmacokinetic interactions listed below are potentially clinically important. Drugs that induce hepatic enzymes such as 
phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids and may require increases in corticosteroid 
dose to achieve the desired response. Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids 
and thus decrease their clearance. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity. Corticosteroids 
may increase the clearance of chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of 
salicylate toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients 
suffering from hypoprothrombinemia. The effect of corticosteroids on oral anticoagulants is variable. There are reports of enhanced 
as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices should be 
monitored to maintain the desired anticoagulant effect. 
 
Information for the Patient 
Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles. 
Patients should also be advised that if they are exposed, medical advice should be sought without delay. 
 
ADVERSE REACTIONS 
Fluid and Electrolyte Disturbances 
Sodium retention 
Fluid retention 
Congestive heart failure in susceptible patients 
Potassium loss 
Hypokalemic alkalosis 
Hypertension 
Musculoskeletal 
Muscle weakness 
Steroid myopathy 
Loss of muscle mass 
Osteoporosis 
Tendon rupture, particularly of the Achilles tendon 
Vertebral compression fractures 
Aseptic necrosis of femoral and humeral heads 
Pathologic fracture of long bones 
Gastrointestinal 
Peptic ulcer with possible perforation and hemorrhage 
Pancreatitis 
Abdominal distention 
Ulcerative esophagitis 
Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT) and alkaline phosphatase have been observed 
following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon 
discontinuation. 
Dermatologic 
Impaired wound healing 
Thin fragile skin 
 
 


 
Petechiae and ecchymoses 
Facial erythema 
Increased sweating 
May suppress reactions to skin tests 
Metabolic 
Negative nitrogen balance due to protein catabolism 
Neurological 
Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment 
Convulsions 
Vertigo 
Headache 
Endocrine 
Menstrual irregularities 
Development of Cushingoid state 
Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness 
Suppression of growth in children 
Decreased carbohydrate tolerance 
Manifestations of latent diabetes mellitus 
Increased requirements for insulin or oral hypoglycemic agents in diabetics 
Ophthalmic 
Posterior subcapsular cataracts 
Increased intraocular pressure 
Glaucoma 
Exophthalmos 
Additional Reactions 
Urticaria and other allergic, anaphylactic or hypersensitivity reactions 
 
DOSAGE AND ADMINISTRATION 
The initial dosage of DELTASONE Tablets may vary from 5 mg to 60 mg of prednisone per day depending on the specific disease 
entity being treated. In situations of less severity lower doses will generally suffice while in selected patients higher initial doses 
may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable 
period of time there is a lack of satisfactory clinical response, DELTASONE should be discontinued and the patient transferred to 
other appropriate therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND 
MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF 
THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial 
drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical 
response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations 
which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease 
process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the 
disease entity under treatment; in this latter situation it may be necessary to increase the dosage of DELTASONE for a period of time 
consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn 
gradually rather than abruptly. 
 
Multiple Sclerosis 
In the treatment of acute exacerbations of multiple sclerosis daily doses of 200 mg of prednisolone for a week followed by 80 mg 
every other day for 1 month have been shown to be effective. (Dosage range is the same for prednisone and prednisolone.) 
 
ADT® (Alternate Day Therapy) 
ADT is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every other morning. The 
purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic dose treatment with the beneficial effects 
of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid 
withdrawal symptoms, and growth suppression in children. 
The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or therapeutic effect of corticoids 
persists longer than their physical presence and metabolic effects and (b) administration of the corticosteroid every other morning 
allows for re-establishment of more nearly normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day. 
A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through the hypothalamus a 
fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol 
inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from 
a low point about 10 pm to a peak level about 6 am. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in 
 
 
 


 
plasma cortisol with maximal levels occurring between 2 am and 8 am. This rise in cortisol dampens ACTH production and in turn 
adrenocortical activity. There is a gradual fall in plasma corticoids during the day with lowest levels occurring about midnight. 
The diurnal rhythm of the HPA axis is lost in Cushing's disease, a syndrome of adrenocortical hyperfunction characterized by obesity 
with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent 
diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical findings of hyperadrenocorticism may be noted during long-term 
pharmacologic dose corticoid therapy administered in conventional daily divided doses. It would appear, then, that a disturbance in 
the diurnal cycle with maintenance of elevated corticoid values during the night may play a significant role in the development of 
undesirable corticoid effects. Escape from these constantly elevated plasma levels for even short periods of time may be instrumental 
in protecting against undesirable pharmacologic effects. 
During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of 
cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of 
treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably 
less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered 
every 6 hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when 
pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenocortical 
suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, 
are considered to be short acting (producing adrenocortical suppression for 1¼ to 1½ days following a single dose) and thus are 
recommended for alternate day therapy. 
The following should be kept in mind when considering alternate day therapy: 
1) Basic principles and indications for corticosteroid therapy should apply. The benefits of ADT should not encourage the 
indiscriminate use of steroids. 
2) ADT is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid therapy is anticipated. 
3) In less severe disease processes in which corticoid therapy is indicated, it may be possible to initiate treatment with ADT. 
More severe disease states usually will require daily divided high dose therapy for initial control of the disease process. The initial 
suppressive dose level should be continued until satisfactory clinical response is obtained, usually four to ten days in the case of many 
allergic and collagen diseases. It is important to keep the period of initial suppressive dose as brief as possible particularly when 
subsequent use of alternate day therapy is intended. 
Once control has been established, two courses are available: (a) change to ADT and then gradually reduce the amount of corticoid 
given every other day or (b) following control of the disease process reduce the daily dose of corticoid to the lowest effective level as 
rapidly as possible and then change over to an alternate day schedule. Theoretically, course (a) may be preferable. 
4) Because of the advantages of ADT, it may be desirable to try patients on this form of therapy who have been on daily corticoids for 
long periods of time (eg, patients with rheumatoid arthritis). Since these patients may already have a suppressed HPA axis, 
establishing them on ADT may be difficult and not always successful. However, it is recommended that regular attempts be made to 
change them over. It may be helpful to triple or even quadruple the daily maintenance dose and administer this every other day rather 
than just doubling the daily dose if difficulty is encountered. Once the patient is again controlled, an attempt should be made to reduce 
this dose to a minimum. 
5) As indicated above, certain corticosteroids, because of their prolonged suppressive effect on adrenal activity, are not recommended 
for alternate day therapy (eg, dexamethasone and betamethasone). 
6) The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous 
corticosteroids suppress adrenocortical activity the least, when given at the time of maximal activity (am). 
7) In using ADT it is important, as in all therapeutic situations to individualize and tailor the therapy to each patient. Complete control 
of symptoms will not be possible in all patients. An explanation of the benefits of ADT will help the patient to understand and tolerate 
the possible flare-up in symptoms which may occur in the latter part of the off-steroid day. Other symptomatic therapy may be added 
or increased at this time if needed. 
8) In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily divided corticoid 
dose for control. Once control is again established alternate day therapy may be re-instituted. 
9) Although many of the undesirable features of corticosteroid therapy can be minimized by ADT, as in any therapeutic situation, the 
physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid therapy is being considered. 
 
HOW SUPPLIED 
DELTASONE Tablets are available in the following strengths and package sizes: 
2.5 mg (pink, round, scored, imprinted DELTASONE 
2.5) Bottles of 100            NDC 0009-0032-01 
5 mg (white, round, scored, imprinted DELTASONE 
5) Bottles of 100            NDC 0009-0045-01 
Bottles of 500            NDC 0009-0045-02 
Bottles of 1000          NDC 0009-0045-16 
10 mg (white, round, scored, imprinted DELTASONE 
10) Bottles of 100            NDC 0009-0193-01 
Bottles of 500            NDC 0009-0193-02 
 


20 mg (peach, round, scored, imprinted DELTASONE 20) 
Bottles of 100            NDC 0009-0165-01 
Bottles of 500            NDC 0009-0165-02 
50 mg (white, round, scored, imprinted DELTASONE 50) 
Bottles of 100            NDC 0009-0388-01 
Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP]. 
 
REFERENCES 
1     Fekety R. Infections associated with corticosteroids and immunosuppressive therapy. In: Gorbach SL, Bartlett JG, Blacklow 
NR, eds. Infectious Diseases. Philadelphia: WBSaunders Company 1992:1050–1. 
 
2     Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticoids. Rev Infect Dis 
1989:11(6):954–63. 
Rx only 
 
LAB-0214-2.0 
Rev August 2006