Clinical trial NCT01973283
Conditions: Major Depressive Disorder Dysthymic Disorder Depressive Disorder, NOS
Sponsor: New York State Psychiatric Institute
Start date: 2014-02-19; Completion date: 2020-12-05
Enrollment: 100 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this open-administration treatment study of citalopram (or duloxetine) is to evaluate the effect of antidepressant medication on treating the syndrome of "frailty" in older adults with depressive symptoms. Patients with significant depressive symptoms (defined as CES-D (Center for Epidemiological Studies - Depression scale) \> 10) and 1 or more symptoms of the frailty syndrome (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) will be evaluated and treated with citalopram (or duloxetine) for 8 weeks to test whether antidepressant medication improves both the syndrome of frailty and depressive symptoms. Patients evaluated at the Adult and Late Life Depression clinic and eligible to participate in the study will be treated with an antidepressant medication and assessed on the primary outcome variables (characteristics of frailty, depressive symptoms) as well as on secondary variables which include cognition (global cognition, episodic memory, executive function), and function (physical mobility, instrumental activities of daily living, and social functioning) prior to treatment initiation and following 8-weeks of treatment. The hypotheses for this protocol predict that we will discover a significant improvement on both frailty characteristics and depressive symptoms in this clinical population when treated with antidepressant medication (citalopram or duloxetine).

Detailed description:
Frailty, "a syndrome of decreased resiliency and reserves", is defined by five characteristics: 1)"shrinking" (definition: unintentional weight loss of \> 10 lbs in prior year, or \> 5% loss of body weight in prior year at follow-up), 2) weakness (definition: grip strength in lowest 20% at baseline, adjusted for gender and BMI), 3) poor endurance/energy (definition: self-report of exhaustion on 2 items on the CES-D), 4) slowness (definition: slowest 20% on timed 4 meter or 15 foot walk, adjusted for gender and standing height), and 5) low physical activity (definition: weighted score of kilocalories expended per week as calculated from the Minnesota Leisure Time Activity questionnaire). Frailty is associated with poor prognosis including hospitalization, falls, worsening disability and mobility, and death.

Data from the Cardiovascular Health Study document the rate of comorbid depressive symptoms in frail older adults (16.2% of older adults with at least 1 frailty characteristic had a CES-D \> 10, including 31% of older adults with 3 or more frailty characteristics, compared to 2.6% of nonfrail older adults) despite study exclusion of individuals who were taking an antidepressant (this is in part why we chose to include patients with a CES-D of \> 10, rather than requiring a diagnosis of a depressive disorder such as major depression or dysthymia for this study). The relationship between frailty and depression however goes beyond this association; the five defining characteristics of frailty (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) overlap significantly with symptoms of geriatric depression (decreased energy and motivation, psychomotor slowing, weight loss, decreased participation in leisure activities).

The proposed study is innovative in that it is focuses on a group of older adults who have been unrepresented (via exclusion criteria) in previous clinical studies (frail older adults with comorbid depressive symptoms), and it treats the comorbid depressive symptoms and targets characteristics of the frailty syndrome in the hopes of altering the prognostic trajectory of this clinical sample. This protocol serves two purposes: 1. It tests the feasibility of recruiting and retaining frail older adults with depressive symptoms in a treatment trial, and 2. It provides pilot data for the effectiveness of an antidepressant medication on treating the characteristics of frailty and the comorbid depressive symptoms.

Arms: arm 1: Participants are treated with a flexible-dose antidepressant medication for a period of 8 weeks.
Interventions: intervention 1: Antidepressant Medication
Intervention descriptions: intervention 1: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.

Protocol documents:
SAP_002.pdf: 
Study Title: Antidepressant Response in the Treatment of Depressive Symptoms and Frailty 
Characteristics in Older Adults 
 
Document Date: 11/9/2012 
 
NCT: 01973283 
 
 


Statistical Analyses: 
The data analyses utilize linear mixed effects regression since this approach can handle missing 
data and the correlation of repeated measurements within the individual. Mixed effects models 
using maximum likelihood estimation provide valid inferences in the presence of ignorable 
nonresponse. I will be trained by Dr. Marcus to use Supermix software written by Donald 
Hedeker and Robert Gibbons for the analysis of longitudinal data using mixed-effects linear 
regression. To test Hypothesis 1, I will use linear mixed effects regression of depression score 
across time as a function of frailty deficit group (those with specific frailty deficits=1, those 
without deficits=0), 3 time dummy variables (time1=1 for week 8 and 0 otherwise, time2=1 for 6 
months and 0 otherwise and time3=1 for 12 months and 0 otherwise) and the interaction of group 
by time dummies, with a random effect for repeated measures within the individual. I will use a 
contrast within this model to estimate and test the significance of the difference in outcomes 
between those with and without deficits at the end of the Acute Phase (8 or 16 weeks). 
Hypotheses 2 (outcome: total frailty characteristics) and 3 (outcomes: WHODAS2.0, SPPB, 
ECog, actigraphy scores; IL-6, CRP, serum albumin levels) will be tested in a similar way. The 
contrasts to test Hypothesis 3 will evaluate the deficit vs. non-deficit differences at 6 months and 
at 12 months (end of the Follow-up). The relationship between baseline impairment in domains 
of cognition and frailty characteristics will also be explored. 
 
The power analysis for Aim 1 and Aim 2 is based upon the calculations for longitudinal 
models given by Hedeker and colleagues, with 4-time points assumed (0, 8 weeks, 6 months and 
12 months) for the trend line. A two-group design and a random-effects structure with random 
slope, residual term and autocorrelated residuals, ICC=0.3 and a 5% attrition rate between each 
pair of assessments are assumed. Tests are 2-tailed with α = .05. To test a between groups linear 
trend effect, 30 subjects per group at baseline will provide sufficient power to test for a moderate 
effect (a between groups difference increasing linearly from 0 at baseline to .6 SD units). I 
recognize the limitations of using pilot studies to guide power calculations for future R01. The 
proposed study however will be sufficiently powered to determine whether the effect size is 
clinically meaningful, i.e. an effect size that is somewhat larger than moderate is likely to be 
clinically meaningful.  

ICF_001.pdf: 
Study Title: Antidepressant Response in the Treatment of Depressive Symptoms and 
Frailty Characteristics in Older Adults 
 
Document Date: 10/18/2016 
 
NCT: 01973283 


	  
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New York State Psychiatric Institute – Columbia University Department of Psychiatry 
 
ANTIDEPRESSANT RESPONSE IN THE TREATMENT OF DEPRESSIVE SYMPTOMS 
AND FRAILTY CHARACTERISTICS IN OLDER ADULTS:  
 
PATIENT CONSENT COVER SHEET: 
 
The following outline is meant to serve as a guide to help you learn about this research study 
and decide whether or not you want to take part. It does not replace the consent form that 
you will be asked to read and sign. The consent includes much more information that will help 
you make a decision about participating in this study. Read the consent form carefully, ask 
questions, and take your time or speak to others if you want to before you make your choice. 
Remember, even if you agree to take part in research you can change your mind at any time. 
§ Purpose: To examine the effect of antidepressant medication on treating depressive 
symptoms and the symptoms of frailty over 12-months (participants who enroll in Dr. 
Rutherford’s 8-week trial entitled, “Antidepressant response in late life depression” [IRB 
6836] will be followed for 10 months after the completion of that study). 
§ Participants: You have been asked to participate in this study because at the time of your 
initial evaluation you reported clinically significant depressive symptoms and one or more 
characteristics consistent with the frailty syndrome including exhaustion, decreased 
energy, weight loss, decreased grip strength, and slow/unsteady gait.  
§ Initial Treatment: You will be treated with either the medication escitalopram (trade name 
Lexapro) or duloxetine (trade name Cymbalta) for eight weeks. 
o Although the Food and Drug Administration approved these medications for the 
treatment of depression, these medications have not been tested to treat frailty.  
o Please discuss the side effects of the medications that are covered in the consent 
form with the study physician before you decide to participate in this study. 
§ Assessment: You will undergo two 90-minute evaluations (at baseline prior to treatment 
and again at Week 8) to assess your memory, day-to-day functioning, physical activity, 
and mobility.  
§ Acute treatment: After the baseline assessment you will begin treatment and come to the 
clinic every week for the next 8 weeks to monitor your progress and side effects.  
§ Following Acute Treatment: After you finish the 8-week trial, you will receive continued 
treatment in our clinic for 10 additional months. Whether you entered the study after 
completion of Dr. Rutherford’s 8-week trial or completed the initial 8-week trial as part of 
this study, you can remain on the treatment that got you better or discuss alternative 
treatment approaches with your study physician including different medications or 
psychotherapy. Given the cost of certain medications, we may ask to use your insurance 
if applicable to cover the cost during the continued treatment phase. If there is a co-pay 
involved, the study will reimburse the cost of the co-pay to you. Two 90-minute 
assessments identical to those conducted at baseline and Week 8 will be conducted 6-
months and 12-months after initial initiation of treatment. 
§ Early Discontinuation: You may stop your participation in the study at any time for any 
reason. Your doctor may take you out of the study if 1) Staying in the study would be 
harmful to you, 2) You need treatment not allowed in the study, or 3) You do not follow 
study procedures.  
§ If you are removed from the study or after you complete the 12-month study, you will be 
treated in the clinic at no cost to you for at least three months or, if you prefer, the clinic 
staff will refer you elsewhere for continued treatment.


	  
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New York State Psychiatric Institute – Columbia University Department of Psychiatry 
 
ANTIDEPRESSANT RESPONSE IN THE TREATMENT OF DEPRESSIVE SYMPTOMS 
AND FRAILTY CHARACTERISTICS IN OLDER ADULTS:  
PATIENT CONSENT FORM 
 
PURPOSE AND OVERVIEW 
 
You are being asked to participate in a study being conducted at the New York State 
Psychiatric Institute to examine the effect of antidepressant medication on treating depressive 
symptoms and the symptoms of the syndrome of frailty. You have been asked to participate 
in this study because you have reported during your initial evaluation clinically significant 
depressive symptoms and one or more characteristics consistent with the frailty syndrome 
including exhaustion, decreased energy, weight loss, decreased grip strength, and 
slow/unsteady gait. For the treatment of your symptoms, you will initially be given either the 
medication escitalopram (trade name Lexapro) or duloxetine (trade name Cymbalta). 
Although escitalopram and duloxetine have been shown to be effective in and are approved 
for the treatment of depression by the Food and Drug Administration, these medications have 
not been tested in the treatment of frailty. As part of this study, you will be asked to take a 
number of tests that assess your memory, physical activity levels, and your day-to-day 
functioning. All procedures will take place at the New York State Psychiatric Institute. The 
purpose of this study is to determine the effect of antidepressant medication on treating 
depressive symptoms and the characteristics of frailty. 
 
If you are entering this study after completing Dr. Rutherford’s 8-week placebo-controlled trial 
entitled, “Antidepressant response in late life depression” (IRB 6836) and you responded to 
this treatment, you can remain on this treatment. If you did not respond to treatment, you can 
discuss alternative treatment approaches with your study physician. If you responded to 
placebo treatment, you can choose to remain off antidepressant treatment and be monitored 
in this study or start antidepressant treatment.  
 
VOLUNTARY 
 
Participation in this research study is voluntary. If you decide not to participate, or if you later 
decide to stop participating, you will not lose any benefits to which you are otherwise entitled.  
A decision not to participate or withdraw your participation will not affect your current or future 
treatment at the New York State Psychiatric Institute or Columbia University.  
 
ALTERNATIVE TO STUDY PARTICIPATION 
You do not have to participate in this study to receive treatment for your depressive 
symptoms. Many other available antidepressant medications have also been shown to be 
effective in the treatment of depressive symptoms. Additionally, some with your symptoms 
may respond to psychotherapy (cognitive-behavioral or problem-solving therapies).  
 
STUDY PROCEDURES 
Stopping your current antidepressant if you are taking one 
If you are not responding to an antidepressant medication that you have taken for at 
least 6 weeks, you will be asked to stop taking the antidepressant medication you are 


	  
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currently on before beginning the study medication (this is called a washout period). Your 
study doctor will speak with you about the length of the washout period, which differs 
depending on which drug you are taking. For example, washout periods for drugs such as 
sertraline (trade name: Zoloft) or Duloxetine (trade name: Cymbalta) are typically 1-week in 
duration; antidepressant medications such as Fluoxetine (trade name: Prozac) can take up to 
4 weeks in duration. Weekly visits will be required for washout periods lasting more than one 
week to evaluate your health and to check for increased symptoms during the washout 
period. You are asked to contact the study team or your study doctor as soon as possible if 
these symptoms cause you any concern.  
 
Cognitive and Function Testing 
You will be asked to take a number of tests that measure cognition and day-to-day 
functioning (e.g., memory, attention, and other thought processes and physical, social, and 
instrumental activities of daily living) at your baseline visit prior to starting the study 
medication, 8 weeks, 6-months, and 12-months following starting study medication. These 
tests are either paper-and-pencil or measure your physical mobility and take about 90 
minutes to complete at both the baseline and Week 8 study visits. Prior to each of these 
visits, you will be asked to wear a watch that assesses the level of your physical activity 
throughout the day and return this watch one week later when you arrive in clinic for your 
next visit. During Weeks 1-7, a study physician will follow-up with you weekly during clinic 
visits to provide clinical management and assess your weekly depressive symptoms, overall 
severity and improvement, and side effect profiles.  
For individuals who enter this study after completing Dr. Rutherford’s study, you will be 
asked to take these tests at 6-months and 12-months following the initiation of study 
medication in Dr. Rutherford’s study; you will have completed baseline and Week 8 
assessments as part of that study. 
 
Treatment 
During the initial 8-week study, you will be given either escitalopram (Lexapro) or 
duloxetine (Cymbalta). You will be asked to come to the clinic every week for visits with the 
study doctors. The baseline and Week 8 evaluation sessions will each last about 2 hours total 
(including the 90 minutes for testing described in the previous section). All other visits will last 
less than 1 hour.  
If you have not taken an adequate dose of escitalopram for treatment of your current 
depressive symptoms, you will be started on escitalopram 10 mg daily for the first four weeks 
and, if necessary, increased to 20 mg daily by Week 4. This dose range is the same as doses 
used in regular clinical practice. The dose will be adjusted based on your clinical response 
and side effects, i.e., if side effects prove to be a problem, the dose will be reduced. If you 
show a consistent and good response before the maximum dose is reached, you will be 
maintained on the dose to which you responded, i.e., less than the maximum dose of 20 mg 
daily. If the study doctor feels that during the course of escitalopram treatment your condition 
worsens significantly, or intolerable side effects occur, the escitalopram will be discontinued 
and you will be treated in the clinic as clinically indicated with other medications. The dosing 
and side effects of duloxetine are explained in this consent form and your study doctor will 
review these with you.  
If you have not responded to an adequate trial of the medication escitalopram given 
within the last year, you will be given the medication duloxetine as your initial treatment in this 
study. Duloxetine has been approved by the FDA for the treatment of depression and is in 


	  
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widespread clinical use. Duloxetine will be given as a single dose, starting at 30 mg daily for 
the first week followed by increasing doses up to a maximum of 90 mg daily during the 8-
week study. If you respond to duloxetine during the study, the dose increases will be stopped 
and you will be maintained on the effective dose (unless worsening again occurs, in which 
case the dose may again be increased). If you develop problematic side effects during the 
trial, the dose may be reduced after you discuss the side effects with your doctor. If your 
doctor finds that during the medication trial your condition worsens significantly, or intolerable 
side effects occur, the duloxetine will be discontinued and you will be treated in the clinic as 
clinically indicated with other medications.  
If you respond to either escitalopram or duloxetine, you will be maintained on this 
treatment regimen and followed monthly for a total of 12-months of treatment. If you do not 
respond to acute phase trial, you will be treated in the clinic for a total of 12-months of 
treatment as clinically indicated with other medications. Given the cost of certain medications, 
we may ask to use your insurance if applicable to cover the cost during this continued 
treatment phase. If the use of your insurance requires a co-pay, the study will reimburse the 
cost of the co-pay to you.  
If you have entered this study following the completion of Dr. Rutherford’s 8-week 
antidepressant trial and you responded to your study medication (escitalopram or duloxetine) 
or placebo, you will be maintained on this treatment regimen and followed monthly for a total 
of 12-months of treatment. If you do not respond to treatment in Dr. Rutherford’s study, you 
will be treated in the clinic for a total of 12-months as clinically indicated with other 
medications.  
As part of this study, the initiation of new psychotherapy will be delayed. You will be 
asked to not start any new psychotherapy during the initial phase of treatment (lasting 8 
weeks). Following the completion of this initial phase of treatment, if you prefer you will then 
be able to begin new psychotherapy.  
If you have entered this study following the completion of Dr. Rutherford’s 8-week 
antidepressant trial and you responded to your study medication or placebo, if you prefer you 
will then be able to begin new psychotherapy.  
The assessment procedures for this study include interviews that will be conducted by 
a psychiatrist, psychologist, and social worker, as well as a research coordinator. If you find 
any questions during the interviews upsetting, you do not have to answer them.  
Although an initial blood work-up for standard laboratory tests was already conducted 
as part of your initial clinic evaluation, follow-up blood work for standard laboratory tests will 
be done at Week 8, 6-months, and 12-months of this study. The total amount of blood taken 
at each visit will be about 20 cc, which is equivalent to about one and a half tablespoons. In 
total, no more than 100 cc of blood will be drawn for the 12-month study.  
If you have entered this study following the completion of Dr. Rutherford’s 8-week 
antidepressant trial, blood work will be conducted at the beginning of this study, 6-months 
and 12-months after the start of initial study medication. 
 
Treatment at the end of the study 
After you complete the 12-month study, you will be treated in the clinic at no cost to 
you for at least three months or, if you prefer, the clinic staff will refer you elsewhere for 
continued treatment. 
 
Stopping the study 


	  
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Your doctor may stop your participation in the study at any time for any reason. You 
may be taken out of the study if: 
1.  Staying in the study would be harmful to you;  
2.  You need treatment not allowed in the study; 
3.  You do not follow study procedures. 
If you are removed from the study, you will be treated in the clinic at no cost to you for at least 
three months or, if you prefer, the clinic staff will refer you elsewhere for continued treatment. 
 
RISKS 
Escitalopram (Lexapro) Risks 
It is possible that you may experience side effects from the medication escitalopram. 
The side effects most commonly reported are: headache, nausea, sexual difficulties 
(decreased sexual ability or desire, ejaculatory delay), somnolence (sleepiness), insomnia 
(difficulty falling or staying asleep), diarrhea, increased sweating, dry mouth, fatigue, 
dizziness, constipation, and decreased appetite.  
Since escitalopram may have the potential to impair judgment, thinking, or motor skills, 
it is stressed that you should not drive or operate complicated machinery until you are 
reasonably certain that the medications do not produce these effects in you. 
Rare side effects that occur with escitalopram also occur with other antidepressants, 
including serious allergic reactions.  If these or other side effects prove to be a problem, your 
doctor will take necessary action in consultation with you, which may include lowering the 
dose or stopping the medication. 
It is also important that you do not abruptly stop taking the medication without first 
discussing this with the doctor. Stopping these medications suddenly may be followed by 
withdrawal symptoms or by a return of the depressive feelings. You have to be cautious 
about drinking alcohol. Any alcohol that you do drink will have a greater impact, that is, one 
drink will feel like two. You must not take monoamine oxidase inhibitor drugs (MAOIs: 
including Nardil, Parnate) during your treatment with escitalopram. This is important because 
serious reactions including death have been reported when MAOIs have been taken along 
with other antidepressant medications.  
 
Duloxetine (Cymbalta) Risks 
 
You may experience side effects while taking duloxetine, the most common of which is 
nausea. For most people, the nausea is mild to moderate, and usually subsides within one to 
two weeks. Other common side effects are dry mouth, constipation, decreased appetite, 
fatigue, sleepiness, and increased sweating. If these or other side effects are intolerable, the 
medication dose will be lowered or stopped completely.  
 
Rare side effects can occur in susceptible patients, including serious allergic reactions.  
If you experience an allergic reaction to duloxetine, such as rash, hives, or itching, you must 
notify your study doctor immediately. Long-term use of duloxetine is associated with 
osteoporosis/osteopenia. You have to be cautious about drinking alcohol. Any alcohol that 
you do drink will have a greater impact, that is, one drink will feel like two. You must not take 
monoamine oxidase inhibitor drugs (MAOIs: including Nardil, Parnate) during your treatment 
with duloxetine. This is important because serious reactions including death have been 
reported when MAOIs have been taken along with other antidepressant medications.  
Medication is being dispensed in non-childproof packages and extra precautions need 
to be taken to keep the medication away from children. 
 


	  
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Other Study Risks 
If you require medications for sleep disturbance during the course of your participation, 
you may be prescribed lorazepam (up to 2 mg daily) or its equivalent, zolpidem (up to 10 
mg), or trazodone (up to 150 mg). These medications have been used to successfully treat 
sleep disturbances.  
 
It is possible that you may experience side effects from these medications. The side 
effects most commonly associated with lorazepam include sedation, somnolence, and falls. 
The side effects most commonly associated with zolpidem include fatigue and drowsiness, 
along with headache or muscle aches. The side effects most commonly associated with 
trazodone include dizziness, drowsiness, headache, and nausea. 
It is possible that the study medicine may have no beneficial effect, and as a result you 
may feel that your depressive symptoms are getting worse. During the washout period, your 
depressive symptoms will not be treated with active medication and may become worse, stay 
the same, or improve. There is the possibility that when the antidepressant medication is 
discontinued your depressive symptoms may worsen and you may experience increasing 
symptoms of depression such as low mood, sleep and appetite disturbance, low energy and 
interest, and the possibility of suicidal feelings. You should inform your doctor immediately if 
this occurs.  
 
Possible side effects that may be associated with obtaining a 1-2 tablespoon blood 
sample include pain, fainting, bruising, light-headedness, and, on rare occasions, infection.  
Precautions will be taken to avoid these difficulties. It also may be upsetting to answer some 
of the questions about how you are managing in your day-to-day life or to answer the pencil-
and-paper tests of your memory. You can however stop these assessments at any point.  
 
BENEFITS 
No benefits can be guaranteed to you as a result of your participation in this study. The 
treatment offered in this study however may help improve your depressive symptoms. If you 
have entered this study following the completion of Dr. Rutherford’s 8-week antidepressant 
trial, you will have access to an additional 10 months of antidepressant treatment (10 months 
of treatment in this study plus three months of additional treatment following the end of this 
study as compared to the three months of additional treatment offered at the end of Dr. 
Rutherford’s study). 
 
CONFIDENTIALITY 
 
Your name and other personal identifying information will be stored in an electronically 
secure database at New York State Psychiatric Institute. All records of participating subjects 
will be kept in a locked room with access provided only to research staff including the 
research coordinator, data entry person, and the Principal Investigator, Dr. Brown. Records 
will be available to research staff, and to Federal, State and Institutional regulatory personnel 
(who may review records as part of routine audits). Each person participating in the study 
receives a coded number and only the researchers have access to the master list identifying 
names and numbers. All data collected will be kept confidential and used for professional 
purposes only (such as data entry and analysis for the presentation of results in scientific 
journals or at scientific conferences). Access to data stored in computers is restricted by 
security measures (passwords). Only the research coordinator, data entry person, and the 
Principal Investigator, Dr. Brown, have access. If you entered this study following completion 
of Dr. Rutherford’s 8-week trial, data from that study corresponding to data collected as part 


	  
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of this study will be shared between Principal Investigators, coordinators, and data entry 
people. Publications using this data will be done in a manner that fully protects the subject’s 
anonymity. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, 
as required by U.S. Law. This Web site will not include information that can identify you.  At 
most, the Web site will include a summary of the results. You can search this Web site at any 
time. 
 
COMPENSATION AND ECONOMIC CONSIDERATIONS 
 
You will not have to pay for any of the medications, medical examinations, or laboratory tests 
that are required for this study. 
 
IN CASE OF INJURY 
 
Compensation for Research Related Injuries: Federal regulations require that the 
investigators inform you about this institute’s policy with regards to compensation and 
payment for treatment of research-related injuries. 
 
In case of injury, New York State Psychiatric Institute will provide short term emergency 
medical treatment, which has been determined to be necessary by New York State 
Psychiatric Institute's doctors, and which is within the capability of New York State Psychiatric 
Institute to provide. In addition, we will provide assistance in arranging follow up care in such 
instances. 
 
New York State Psychiatric Institute and Research Foundation for Mental Hygiene do not 
provide compensation or payment for treatment of research related injuries.  However, you 
should be aware that you do not give up your legal right to seek such compensation through 
the court by participating in this research. 
 
QUESTIONS 
 
You will be notified of significant new findings that may relate to your willingness to continue 
to participate as a study informant. You have been given a copy of this consent to keep. 
 
Your participation is voluntary, and you can discontinue the evaluation at any time. 
 
You are free to contact the Principal Investigator, Dr. Patrick Brown (646-774-8666) with any 
questions you may have about this study. 
 
If you have any questions about your rights as a research participant, want to provide 
feedback, or have a complaint, you may call the NYSPI Institutional Review Board (IRB). (An 
IRB is a committee that protects the rights of participants in research studies). You may call 
the IRB Main Office at (646) 774-7155 during regular office hours.  
 
DOCUMENTATION OF CONSENT 
 
I have read the above and voluntarily agree to participate in the research study described 
above. 


	  
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Print name:  _____________________ 
 
 
Signed:  
_____________________ 
 
Date:   
_____________________ 
 
I have discussed the proposed research with this participant including the risks, benefits, and 
alternatives to participation (including the alternative of not participating in the research).  The 
participant has had an opportunity to ask questions and in my opinion is capable of freely 
consenting to participate in this research. 
 
 
Print name:  _____________________ 
Person Designated to Obtain Consent  
 
 
Signed:  
_____________________ 
 
Date:   
_____________________ 
 
 

Prot_000.pdf: 
Study Title: Antidepressant Response in the Treatment of Depressive Symptoms and 
Frailty Characteristics in Older Adults 
 
Document Date: 4/6/2020 
 
NCT: 01973283 


Protocol Summary Form
7289R
Brown, Patrick
Page 1 of 22
Protocol Title:
Antidepressant Response in the Treatment 
of Depressive Symptoms and Frailty 
Characteristics in Older Adults (formerly 
#6470)
Protocol Number:
7289R
First Approval:
05/13/2016
Expiration Date:
05/01/2021
Version Date:
04/06/2020
Clinic:
Clinic for Aging, Anxiety, and Mood 
Disorders
Contact Principal Investigator:
Patrick Brown, PHD
Email: Patrick.Brown@nyspi.columbia.edu
Telephone: 6467748666
Research Chief:
Davangere Devanand, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am submitting an annual continuation with modifications
Division & Personnel
Division
What Division/Department does the PI belong to?
Geriatric Psychiatry 
Within the division/department, what Center or group are you affiliated with, if any? 
Adult and Late Life Depression Research Clinic
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
There are no personnel participating in the clinical research outlined in this protocol that are not affiliated 


Protocol Summary Form
7289R
Brown, Patrick
Page 2 of 22
with NYSPI/CU. 
Amendment
Describe the change(s) being made 
We would like permission to send plasma samples to our colleague Dr. Jennifer Felger at Emory University 
to conduct testing on these samples. Dr. Felger's laboratory will only be used as a service, and no 
identifiable data will be shared with her laboratory. 
Provide the rationale for the change(s) 
Given problems with the reliability of the laboratory where we have previously sent plasma samples for 
inflammatory marker measurement, we would like to change the laboratory performing these measurements 
to Dr. Jennifer Felger's lab at Emory University. 
Comment on the extent to which the proposed change(s) alter or affect risks/benefits to subjects 
N/A
Comment on if the proposed change(s) require a modification to the Consent Form (CF)
N/A
Application for Continuation of Research
Status
Current Status of Study: 
All research interventions were completed. Only data analysis is ongoing.
Summary of Experiences to Date
Please provide a summary of scientific progress of the study and the experience of research participants, to 
date. This requirement is designed to allow for the investigator and the IRB to reassess the study’s risks and 
benefits in terms of developments in the field, changing practice patterns, and new IRB policies and 
procedures.
The study has progressed well to date. Potential subjects found the study interesting and agreed to 
participate at high rates. Ninety-three participants signed consent for this protocol. Enrollment has closed 
and all study visits have been completed. There have been no other policy or procedure issues in the study.
Funding
Have there been any changes in funding status since the prior approval? 
No
Have the principal investigator and other investigators made all required disclosures of financial interest in 
the study sponsor/product?
Yes
Summary


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Have there been any study findings, recent literature, or untoward events occuring here or at other sites in 
the past year which might affect the analysis of the safety, risks or benefits of study participation? 
No
Have there been any serious adverse events (serious and/or unanticipated problems involving risks to 
subjects or others at this site which occured in the past year)? 
No
Have all study staff with a significant role in the design or implementation of the human subject components 
of this study received required training in human research subject protections?
Yes
Is the study covered by a certificate of confidentiality? 
No
Overall Progress
Approved sample size
60
Total number of participants enrolled to date
93
Number of participants who have completed the study to date 
72
Have there been any significant deviations from the anticipated study recruitment, retention or completion 
estimates? 
Yes
Describe actions taken or planned to address these problems. 
We have more participants enrolled (93) than originally anticipated (60). After the May 2018 ACAR we 
increased expected enrollment to 85 subjects, anticipating that 60 would complete the 12-month protocol. At 
this time 72 participants have completed the study. A protocol violation was submitted in April 2019 to 
address the over-enrollment and no new patients have enrolled in the study since. 
Comments / additional information 
N/A
Sample Demographics
Specify population
Depressed adults
Total number of participants enrolled from this population to date 
93
Gender, Racial and Ethnic Breakdown 
Gender:
Female: 59
Male: 33
Not specified/missing: 1
  
Ethnicity: 


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Hispanic/Latino: 13
Not Hispanic/Latino: 79 
Not specified/missing: 1
 
Race:
American Indian/Alaska Native: 1 
Asian: 1 
Black/African-American: 15
Native Hawaiian/Pacific Islander: 0 
White: 65
More than one: 4
Don't know: 4
Not specified/missing: 3 
Summary of Current Year's Enrollment and Drop-out 
Number of participants who signed consent in the past year
0
Did the investigator withdraw participants from the study? 
No
Did participants decide to discontinue study involvement? 
No
Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Psychiatric Assessment
   Neuropsychological Evaluation
   Collection of Biological Specimens
   Medication Trial
   Off-label Use of Drug or Device
Population
Indicate which of the following populations will be included in this research
   Adults over 50


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Research Support/Funding
Will an existing internal account be used to support the project?
No
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract is currently funded
Source of Funding
Federal
Institute/Agency
NIMH
Grant Name
The Phenomenology and Antidepressant Treatment of Depressed, Frail Older Adults 
Grant Number
1 K23 MH099097-01A1
Select one of the following
Single Site
Business Office
RFMH
Does the grant/contract involve a subcontract? 
No
Study Location
Indicate if the research is/will be conducted at any of the following
   NYSPI
This protocol describes research conducted by the PI at other facilities/locations
No
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
      The goal of this open-administration treatment study of escitalopram (or duloxetine) is to
evaluate the effect of antidepressant medication on treating the syndrome of “frailty” in older adults
with depressive symptoms. Patients with significant depressive symptoms (DSM-IV diagnosis of


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dysthymia or Major Depression with a Hamilton Rating Scale for Depression (HRSD) > 16) and 1 or more 
symptoms of the frailty syndrome (exhaustion, decreased energy, weight loss, decreased grip strength, 
and slow/unsteady gait) will be evaluated and treated with escitalopram (or duloxetine) for 8 weeks to test 
whether antidepressant medication improves both the syndrome of frailty and depressive
symptoms. Because these patients have a diagnosis of major depression or dysthymia, there is a
responsibility to first and foremost ensure that patients achieve measurable improvement in
depressive symptoms. For this reason, remission of symptoms (8-Week HRSD<10) is the clinical
goal. All patients will continue in the protocol for a total of 12-months (Follow-up Phase). Patients who 
remit to the Acute Phase trial will be maintained on their treatment regimen and followed monthly. Patients 
who do not remit to the Acute Phase trial will be treated as clinically indicated (i.e. augmentation strategies) 
in the Adult and Late Life Depression Clinic (ALLDC) during the Follow-up Phase.
      Patients who had a DSM-IV diagnosis of Major Depression with a HRSD> 16 and 1 or more
frailty characteristics at their initial evaluation who entered study 6836 and completed an 8-week
placebo control trial will have the option to enter this study following the completion of 6836. If the
patient remitted to treatment in 6836, they will remain on that treatment and monitored as part of
protocol 7289R (formerly #6470). If the patient did not remit to treatment in 6836, patients can discuss 
alternative treatment strategies with the study psychiatrists and will be treated openly as part of this 
protocol. Patients who respond to placebo as part of 6836 will be given the option of remaining off 
medication and being monitored through this protocol's follow-up phase, or starting treatment as clinically 
indicated as part of this protocol. 
      Patients evaluated at the Adult and Late Life Depression Clinic and eligible to participate in the 
study will be treated with an antidepressant medication and assessed on the primary outcome variables
(characteristics of frailty, depressive symptoms) as well as on secondary variables which include 
cognition (global cognition, episodic memory, executive function), and function (physical 
mobility/activity, instrumental activities of daily living, and social functioning) prior to treatment initiation 
and at the end of an Acute Phase trial (Week 8); during the Follow-up Phase, patients will have monthly 
assessments in the ALLDC, and full assessment batteries at 6- and 12-months post treatment initiation.
Background, Significance and Rationale
Background, Significance and Rationale
      Frailty, “a syndrome of decreased resiliency and reserves”, is defined by five characteristics: 
1)“shrinking” (definition: unintentional weight loss of > 10 lbs in prior year, or > 5%
loss of body weight in prior year at follow-up), 2) weakness (definition: grip strength in lowest 20%
at baseline, adjusted for gender and BMI), 3) poor endurance/energy (definition: self-report of
exhaustion on 2 items on the Center for Epidemiologic Studies Depression Scale (CES-D), 4) slowness 
(definition: slowest 20% on timed 4 meter or 15
foot walk, adjusted for gender and standing height), and 5) low physical activity (definition:
weighted score of kilocalories expended per week as calculated from the Minnesota Leisure Time
Activity questionnaire). Frailty is associated with poor prognosis including hospitalization, falls,
worsening disability and mobility, and death.
 
      There is a relationship between frailty and depression, as the five defining characteristics of frailty 
(exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) overlap 


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significantly with symptoms of geriatric depression (decreased energy and motivation, psychomotor 
slowing, weight loss, decreased participation in leisure activities). Despite the strong association between 
depression and the syndrome of frailty, there are currently no clinical studies being funded by the NIMH or 
NIA on the association between depression and frailty in late life (NIH’s RePORTER system). In fact, the 
clinical studies of frail older adults that have been funded (primarily exercise trials for frail older adults) 
have excluded depression (Brown et al., 2000, Binder et al., 2005). The proposed study is innovative in that 
it is focused on a group of older adults who have been unrepresented (via exclusion criteria) in previous 
clinical studies (frail older adults with comorbid depressive illness), and it treats the depressive symptoms 
and targets characteristics of the frailty syndrome in the hopes of altering the prognostic trajectory of this 
clinical sample. This protocol serves two purposes: 1. It tests the feasibility of recruiting and retaining frail 
older adults with a depressive illness in a treatment trial, and 2. It provides pilot data for the effectiveness of 
an antidepressant medication on treating the characteristics of frailty and the comorbid depressive 
symptoms.
Specific Aims and Hypotheses
Specific Aims and Hypotheses
Specific Aims and Hypotheses 
 
The hypotheses for this protocol predict that we will discover a significant improvement on both
frailty characteristics and depressive symptoms in this clinical population when treated with
antidepressant medication (escitalopram or duloxetine).
 
Specific Aim: Evaluate the effect of antidepressant medication on treating the syndrome of frailty
and depressive symptoms in an older adult sample.
 
   Hypothesis 1: Patients on antidepressant medication will show improvements in frailty
characteristics 8-weeks after treatment implementation.
 
   Hypothesis 2: Patients on antidepressant medication will show improvements in
depressive symptomatology (Week 8 Hamilton Rating Scale – Depression, HRSD < 10) 8-weeks
after treatment implementation.
 
   Hypothesis 3: Patients on antidepressant medication will show improvements in secondary
outcomes including physical activity/mobility and instrumental activities of daily living 6 months
and 12-months after treatment implementation.
Description of Subject Population
Sample #1


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Specify subject population
Older adults with characteristics of frailty and depressive illness
Number of completers required to accomplish study aims
60
Projected number of subjects who will be enrolled to obtain required number of completers
85
Age range of subject population
60-95 years 
Gender, Racial and Ethnic Breakdown
Based on previous depression studies conducted in the Adult and Late Life Depression Clinic, we expect a 
gender distribution of approximately 60% female and 40% male. We expect an ethnic breakdown of 
approximately 75% Caucasian, 15% African American, and 10% Hispanic.
 
No patients who meet study criteria will be excluded from study participation on the basis of gender or 
ethnicity.
 
 
Description of subject population
N = 60
- frailty characteristics > 1 
 
AND
 
- DSM diagnosis of MDD or dysthymia with a HRSD>16, Age range 60-95 years  
Recruitment Procedures
Describe settings where recruitment will occur
Patients will be recruited from the Adult and Late Life Depression Clinic (ALLDC)
at the New York State Psychiatric Institute (NYSPI).
How and by whom will subjects be approached and/or recruited? 
Patients will be evaluated via the ALLDC evaluation (protocol #7284R) as well as for the frailty
characteristics and, if eligible and interested in participating, enrolled into this protocol. If eligible
the person doing the initial evaluation (including Patrick J. Brown, Ph.D., Bret Rutherford, M.D., Steven 
Roose, M.D., and Allegra Broft, M.D.) will briefly describe the current protocol to the patient. If the patient 
expresses interest in participating, Dr. Brown will speak with the patient about the current protocol. If 
patient is willing to participate, informed consent will be obtained.
 


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For patients who are enrolled in Dr. Rutherford’s study (6836): During the Week 5 visit of the 8-week
acute trial that Dr. Rutherford is conducting, the treating physician will mention that there is currently a
study ongoing that patients can enroll in at the end of the 8-week trial that will allow for continued follow-
up care and antidepressant treatment for 10 more months (10-months in 7289R (formerly #6470) plus 3-
months of open treatment as compared to 3-months of open treatment following the completion of Dr. 
Rutherford’s study). If the patient is interested, a non-study physician will speak with the patient in detail 
about study 7289R (formerly #6470) at the end of their Week 5 visit. 
How will the study be advertised/publicized? 
Letters will be sent to geriatricians and senior citizen centers, ads will be placed in
local publications and fliers at local businesses and senior centers. Additionally, we will post our study on 
RecruitMe, CUMC’s new tool for listing clinical trials and other human subjects studies. 
Do you have ads/recruitment material requiring review at this time? 
Yes
Does this study involve a clinical trial?
Yes
Please provide the NCT Registration Number
NCT01973283
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
Yes
Describe concurrent research involvement
Because treatment strategy in this current protocol mirrors the treatment strategies used in other
protocols conducted in the ALLDC, subjects who meet criteria for this and other protocols in the
ALLDC can participate in both protocols concurrently. These protocols are listed below:
 
   - MECHANISMS OF ANTIDEPRESSANT NONRESPONSE IN LATE LIFE DEPRESSION (PI 
     Rutherford) - IRB #6836
   - PHYSICAL AND MENTAL FATIGABILITY IN LATE LIFE CLINICAL POPULATIONS (PI 
     Brown) - IRB #7360
   - FLAVANOL AUGMENTATION FOR ANTIDEPRESSANT NON-RESPONSIVE LATE LIFE 
     DEPRESSION (PI Rutherford) - IRB #7368 
   - A STUDY OF L-DOPA FOR DEPRESSION AND SLOWING IN OLDER ADULTS (PI 
     Rutherford) -      IRB #7270
   - MITOCHONDRIAL FUNCTION, FATIGUE, AND DEPRESSION IN LATER LIFE (PI Brown)      - 
IRB #7379
   - OPTIMIZING OUTCOMES OF TREATMENT-RESISTANT DEPRSESION IN OLDER    ADULTS 
(OPTIMUM) STUDY (PI Roose) - IRB #7409
   - TREATING HEARING LOSS TO IMPROVE MOOD AND COGNITION IN OLDER ADULTS(PI 
   Rutherford) - IRB #7540
   - L-DOPA VS. PLACEBO FOR DEPRESSION AND PSYCHOMOTOR SLOWING IN OLDER 
ADULTS (PI Rutherford) - IRB #7733
    


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 Subjects may also participate in the following protocols outside of the ALLDC if eligible:
   - OLFACTORY DEFICITS AND DONEPEZIL TREATMENT IN COGNITIVELY IMPAIRED 
   ELDERLY (PI Devanand) - IRB #6655 
 
The consent form for this study is separate from those from the above protocols. Participation in
this study will not affect their participation in the other study. This is made explicit in the consent
form for this study.
Inclusion/Exclusion Criteria
Name the subject group/sub sample
Older adults with frailty characteristics and depressive symptoms 
Create or insert table to describe the inclusion criteria and methods to ascertain them
At the time of initial clinic evaluation*:
Anyone with 1 or more characteristics of frailty (frailty evaluation)
A HRSD>16 and a DSM-IV depressive disorder (e.g., MDD, Dysthymia) (HRSD, SCID) 
Capable of providing informed consent (clinical interview)
Currently followed by a PCP (had an eval in last 6-months) (patient report)
o Patient required to provide release of information to facilitate communication with PCP 
 
* Patients who enroll in Dr. Rutherford's 8-week placebo control antidepressant trial (6836) are
eligible for enrollment following the completion of that trial regardless of treatment outcome if they
met the above criteria during their initial clinic evaluation. Patients who responded to treatment in
study 6836 and may no longer meet the severity criteria (HRSD > 16) at the time they provide
informed consent for 7289R (formerly #6470) are still eligible to enroll in 7289R (formerly #6470) as long 
as they met the above criteria at their initial clinic evaluation prior to their enrollment in 6836. 
 
 
Create or insert table to describe the exclusion criteria and methods to ascertain them
Acute cancer treatment (clinical interview)
Acute, severe or unstable medical illness (clinical interview)
End stage medical illness (e.g. liver, kidney, pulmonary) (clinical interview)
Mini Mental Exam < 24 or a diagnosis of dementia (clinical interview, MMSE)
Individuals who do not have capacity to consent (clinical interview)
Diagnosis of substance abuse or dependence (last 12 months) (clinical interview, SCID)
o Excluding Nicotine dependence
History of psychosis or bipolar disorder (clinical interview, SCID)
Patient is considered a significant risk of suicide (clinical judgment, HRSD)


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Subject is considered based on history to be unlikely to respond to the single agent escitalopram or 
duloxetine (i.e., subjects with treatment resistant depression, including subjects with previous 
treatment with ECT) (clinical interview, SCID)
History of allergic or adverse reaction to escitalopram or duloxetine, or non-response to adequate 
trial of escitalorpam (at least 4 weeks at dose of 20 mg) or duloxetine (at least 4 weeks at dose of 90 
mg) (clinical interview)
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
No
Waiver of documentation of consent 
No
Waiver of parental consent 
No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
Yes
Indicate NYSPI IRB # 
7284R 
Describe Study Consent Procedures
Step 1. Patients will undergo a medical, psychosocial, and psychiatric evaluation by a clinic
physician as part of the evaluation procedures for the ALLDC (protocol # 7284R). As per #7284R,
the five frailty characteristics will be assessed during this initial evaluation.
 
Step 2*. If the patient meets inclusion/exclusion criteria for this current study, the evaluating
physician will briefly describe the study. If patient expresses interest in participating, Dr. Brown will
speak with the patient about the current protocol. If patient is willing to participate in this protocol,
informed consent will be obtained. At this time, a signed release of information form will also be
obtained so that the study physician can communicate with the patient’s internist or Primary Care
Physician prior to treatment initiation and during the study. We respect that this clinical population
may have multiple medical issues that contribute to their clinical presentation of frailty and to their
comorbid depressive symptoms. As such, an ongoing communication with their primary physician
is necessary. If patient is unwilling to participate in this protocol, this will not affect his/her standing
in ongoing research protocols within the clinic.


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* For patients who are enrolled in study 6836: During the Week 5 visit of the 8-week acute trial that
Dr. Rutherford is conducting, the treating physician will mention that there is currently a study
ongoing that patients can enroll in at the end of the 8-week trial that will allow for continued followup
care and antidepressant treatment for 10 more months (10-months in 7289R (formerly #6470) plus 3-months 
of open treatment as compared to 3-months of open treatment following the completion of Dr. 
Rutherford’s study). If the patient is interested, a non-study physician will speak with the patient in detail 
about study 7289R (formerly #6470) at the end of their Week 5 visit. If patient is willing to participate in 
this protocol, informed consent will be obtained. 
 
Step 3. Patients will return for a baseline assessment (See Study Procedures for details). 
 
Capacity to consent: 
      Patients who would have capacity issues (e.g. dementia, psychotic depression) are excluded from this 
study.
 
Indicate which of the following are employed as a part of screening or main study consent procedures
   Consent Form
Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Broft, Allegra, MD
Roose, Steven, MD
Rutherford, Bret, MD
Type in the name(s) not found in the above list
Study Procedures
Describe the procedures required for this study
Drug Washout:
If patients are currently on antidepressant medication, have been for at least 6 weeks, and
are not responding (defined as depressive symptoms as measured at baseline by the Hamilton
Rating Scale for Depression, HRSD, are > 14), they may be eligible to enter this study. Those who
decide to participate will be asked to stop taking the antidepressant medication they are currently
on before beginning the study medication (washout period). The study psychiatrist or nurse practitioner will 
speak with the patient about the length of the washout period, which differs depending on which drug they 
are taking. Weekly visits are required for washout periods lasting more than one week to evaluate the 
patient’s health and to check for increased symptoms during the washout period. The patient’s health will be 


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monitored using a clinical interview and the Treatment Emergent Signs and Symptoms (TESS) scale both 
conducted by the study physician or nurse practitioner, and the patient’s symptoms will be monitored by the 
HRSD which will be conducted by either the study physician, nurse practitioner or a trained rater. Follow-
up by the study physician or nurse practitioner will occur weekly during the washout period, and, while 
follow-up can be conducted via telephone, patients will not go more than 2 weeks during the washout period 
without an in-person clinic follow-up evaluation. Patients will be instructed to contact the study doctor or 
nurse practitioner for any concern.
 
Psychotherapy:
         During the 8-week Acute Phase of the study, patients will not be allowed to begin new psychotherapy. 
If they are currently in stable psychotherapy and have been for 3 months or more, they will be eligible to 
participate in this study and may continue psychotherapy during the study. Following the Acute Phase of 
treatment, however, patients may start new psychotherapy as it is not reasonable to prohibit potential 
treatments from patients for a full 12-months. If patients start psychotherapy during the Follow-up phase, it 
will be noted in the patient's chart and in the database.  
 
Prior to Baseline: 
 Patients physical activity levels will be measured prior to treatment initiation via the use of
actigraphy watches. Patients who meet study criteria at initial evaluation and provide informed
consent to participate in the study protocol will be taught how to use the actigraphy watches for
the week in between initial evaluation and baseline visits. The watches will record total daily
activity levels via expended kcal and the data will be uploaded into the database when the
watches are returned at the Baseline visit.
* Patients who enter protocol this study via the completion of protocol 6836 will not participate in the 
actigraphy assessment procedures throughout the study.
 
Baseline:
Patients who meet study criteria at initial evaluation and provide informed consent to
participate in the study protocol will complete a baseline assessment prior to treatment initiation.
This 90-minute assessment includes: Recording the patient’s height and weight, vital signs
(including blood pressure, heart rate, and postural changes), blood work (including inflammatory
markers [C-reactive protein, CRP, and Interleukin 6, IL 6] and albumin levels), a depression
evaluation (HRSD), a function evaluation (World Health Organization Disability Assessment Scale 2, 
WHODAS2, the Measure of Everyday Cognition, ECog, and the Short Physical Performance Battery, 
SPPB), and a brief cognitive evaluation (Logical Memory Wechsler Memory Scale (WMS) III, Stroop 
Color-Word test, Trailmaking Test A & B, and Wechsler Adult Intelligence Scale - Revised (WAIS-R) 
Digit Symbol Test). A study psychiatrist or nurse practitioner will assess patients’ side effect profiles using 
the modified Treatment Emergent Signs and Symptoms (TESS) scale, and overall severity using Clinical 
Global Impression – Improvement (CGI-I) ratings. Given the fact that the patients in this protocol by 
definition may experience exhaustion, deceased energy and/or motivation the patient will be told that they 
can request a rest at any time and will be asked if they need a break every 15 minutes. If necessary the 
evaluation session can be divided into 2 separate 45-minute sessions. 
* Patients who enter this study via the completion of protocol 6836 will have completed baseline testing as 
part of protocol 6836.
 


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Dosing Schedule for Acute Phase:
Escitalopram: 10 mg of escitalopram daily for first 4 weeks, and, if patients do not meet remission
criteria (HRSD < 10) or patients continue to report depressive symptoms, are tolerating the medication well, 
and wish to try a higher dose, 20 mg daily for final 4 weeks.
  
Duloxetine: If patients have previously failed a trial of escitalopram, they will be treated with duloxetine: 30 
mg daily for the first week, then 60 mg for the next four weeks, and, if patients do not meet remission 
criteria or patients continue to report depressive symptoms, are tolerating the medication well, and wish to 
try a higher dose, the dose is increased to 90 mg for the final three weeks.  
 
* Patients who enter this study via the completion of protocol 6836 who were treated with placebo and did 
not respond and who have no history of unsuccessful treatment with escitalopram will be treated with 
escitalopram via the above dosing schedule.
* Patients who remitted to escitalopram or duloxetine as part of 6836 will be maintained on their treatment 
upon entering this protocol and monitored via the study protocol.
* Patients who remitted to placebo treatment will have the option of being monitored without
treatment or starting antidepressant treatment as part of this protocol; those who choose to be 
monitored without treatment will have the option of starting antidepressant treatment should symptoms 
worsen.
* The study physician or nurse practitioner will discuss alternative treatment strategies with patients who 
did not remit to escitalopram or duloxetine as part of study 6836. 
*If patients require medications for sleep disturbance during the course of their participation, they will be 
prescribed lorazepam (up to 2 mg daily) or its equivalent, zolpidem (up to 10 mg), or trazodone (up to 150 
mg). These medications have been used to successfully treat sleep disturbances. 
It is possible that patients may experience side effects from these medications. The side effects most 
commonly associated with lorazepam include sedation, somnolence, and falls. The side effects most 
commonly associated with zolpidem include fatigue and drowsiness, along with headache or muscle aches. 
The side effects most commonly associated with trazodone include dizziness, drowsiness, headache, and 
nausea.
 
Follow-up during Acute Phase:
Following the baseline assessment, patients will be followed up weekly in clinic for the
duration of the Acute Phase of treatment (8-weeks). Patients will receive clinical management and complete 
follow-up HRSD, CGI-I, and TESS by trained raters to monitor weekly depression levels, improvement, and 
side effect profiles. During follow-up clinic visits, vital signs (blood pressure, heart rate, and postural 
changes) will be collected. 
 
WEEK 7: In addition to the standard weekly clinic follow-up procedures, patients will again be provided 
actigraphy watches to record their physical activity levels at the end of the acute medication trial. Patients 
will wear actigraphy watches throughout the period between Week 7 and Week 8 and return the watches 
when they arrive for their full assessment procedures at Week 8.
 
WEEK 8: At Week 8 of an Acute Trial, patients will undergo the same 90-minute assessment that


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was conducted at baseline with an additional reassessment of the frailty characteristics:
Recording the patient’s height and weight, blood work (including inflammatory markers [C-reactive
protein, CRP, and Interleukin 6, IL 6] and albumin levels), a depression evaluation (HRSD), a function 
evaluation (World Health Organization Disability Assessment Scale 2, WHODAS2, the Measure of 
Everyday Cognition, ECog, and the Short Physical Performance Battery, SPPB), and a brief cognitive 
evaluation (Logical Memory WMS III, Stroop Color-Word test, Trailmaking Test A & B, and Wechsler 
Adult Intelligence Scale - Revised (WAIS-R) Digit Symbol Test) along with a Week 8 TESS and final CGI-
I. The Week 8 assessment will take 2 hours total and as at baseline may require frequent breaks or 
be divided into two sessions if necessary. Week 8 assessments for those patients who enter this protocol via 
study 6836 will be conducted as part of study 6836.
 
Follow-up Phase:
At the end of the acute treatment trial, all patients will continue into the Follow-up Phase.
Patients who remit to the Acute Phase trial will be maintained on their treatment regimen
and followed monthly. Patients who do not remit to the Acute Phase trial will be treated and
followed as clinically indicated (i.e. augmentation strategies, etc.) in the ALLDC. During the
Follow-up Phase, patients will have monthly assessments in the ALLDC with procedures that
mirror the weekly assessment procedures from the Acute Phase Trial. If more frequent follow-up
visits are clinically indicated by the treatment strategy during the Follow-up Phase, more frequent
follow-up visits will be conducted. Full assessment batteries (as described in the Baseline and
Week 8 subsections above) will be repeated at 6- and 12-months following patients' initial baseline
visit. Physical activity levels via actigraphy will be assessed over the course of the week leading
up to the 6-month and 12-month full assessment visits.
Psychological assessments performed on study participants by a psychiatrist or nurse practitioner, may also 
be performed by medical psychiatry interns (PGY-1) who come to our clinic for 4-week rotations. All 
medical interns will have completed NYSPI-specific CITI training for human subjects research (specifically 
the biomed or social/behavioral course). 
 
Study assessments and prescribing of drugs to study participants may also be done by a Psychiatric Nurse 
practitioner, Galit Sharon Marcus, who has completed NYSPI-specific CITI training for human subjects 
research (specifically the biomed or social/behavioral course and Good Clinical Practice.  
 
The NP is licensed and board certified as a Psychiatric and Mental Health NP. She has considerable 
experience in working with a late-life population but no prior research experience in this population. That is 
why she will have an extended period of time where all her work is directly in-person supervised. The NP 
will have a lengthy orientation
where she will be observing evaluations done by Drs. Roose, Rutherford, Brown and Broft. She will then do 
evaluations under the observation of the same MDs. Even when she is doing evaluations and follow-ups by 
herself, all cases are reviewed weekly at a clinic meeting. Even after orientation is over, it is the practice of 
the clinic that the doctors consult with and present cases to each other so all patients are essentially treated 
by the entire clinic team.
 
 
 Following the completion of the 12-month study, patients will be treated in the clinic at no cost to them


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for at least three months or, if they prefer, the clinic staff will refer them elsewhere for continued
treatment. 
 
You can upload charts or diagrams if any
Criteria for Early Discontinuation  
Criteria for Early Discontinuation
Criteria for Early Discontinuation
 
         If the study doctor feels that during the course of escitalopram or duloxetine treatment the patient’s 
condition worsens significantly, or intolerable side effects occur, the study medication will be discontinued 
and the patient will be treated in the clinic as clinically indicated with other medications. 
 
The study doctor may stop patient participation in the study at any time for reasons such as,
for example, staying in the study would be harmful to patients, patients need treatment not
allowed in the study, or patients do not follow study procedures. During the follow-up period,
patients will be discontinued from the acute treatment phase if there is a rating of 6 (much worse)
or 7 (very much worse) on the CGI-I for 2 consecutive weeks. No further research measures will
be performed on patient dropped from the study. These patients will be evaluated weekly in the
clinic following discontinuation. If patients are removed from the study, they will be treated in the
clinic at no cost to them for at least three months or, if they prefer, the clinic staff will refer them
elsewhere for continued treatment.
 
If a patient discontinues medication due to tolerability problems, ineffectiveness, patient
preference, or other reasons, the patient will be dropped out of the study and followed in the clinic
for 3 months. Appropriate medication options will be discussed with the patient based on their
symptoms and history. If the patient wishes, they will be provided referrals for psychotherapy or
treatment options outside of our research clinic. No further research measures will be conducted
once a patient discontinues study participation. If a patient discontinues treatment but is
willing to continue participation in study assessments, the patient will continue to be
followed and monitored as per the assessment schedule outlined in this PSF. 
Blood and other Biological Samples
Please create or insert a table describing the proposed collection of blood or other biological specimens
Evaluation/Baseline: CBC, blood chemistries, and electrolytes as well as inflammatory markers
(C-reactive protein, Interleukin 6), Serum 25-hydroxyvitamin D level, and Albumin levels.
 
Week 8: CBC, blood chemistries, and electrolytes as well as inflammatory markers (C-reactive


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protein, Interleukin 6), Serum 25-hydroxyvitamin D level, and Albumin levels
 
6-Months: CBC, blood chemistries, and electrolytes as well as inflammatory markers (C-reactive
protein, Interleukin 6), Serum 25-hydroxyvitamin D level, and Albumin levels
 
12-Months: CBC, blood chemistries, and electrolytes as well as inflammatory markers (C-reactive
protein, Interleukin 6), Serum 25-hydroxyvitamin D level, and Albumin levels
 
The total amount of blood drawn per visit should be no greater than 20 cc. The total amount of
blood for the entire study should not exceed 100 cc. 
 
Plasma samples will be sent to Dr. Jennifer Felger at Emory University to conduct testing. Dr. 
Felger's laboratory will be used only as a service, with no identifiable data being shared.
Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment
Frailty criteria assessment at Clinic Evaluation, Week 8, Month 6, and Month 12:             20 minutes
o Exhaustion (CES-D items “I felt that everything I did was an effort” and “I could not get 
going”),
o Weight loss (patient report of 10 lb loss unintentionally in last year)
o Weak grip strength (via hand dynamometer; stratified by gender and body mass index)
o Slow walking speed, (15 feet speed stratified by gender and height)
o Low energy expenditure (Short version of the Minnesota Leisure Time Activity 
questionnaire. Kcals per week expended are calculated using standardized algorithm and 
stratified by gender).
Hamilton Rating Scale for Depression:                                                                                 15 minutes
o Conducted at each follow-up visit
UCLA Revised Loneliness Scale:                                                                                           1 minute
o Self report form
90 minute assessment at the Baseline, Week 8, Month 6, and Month 12 Visits consists of:
o Height and Weight and blood work                                                                             
10 minutes
Includes:
C-reactive protein, CRP, Interleukin 6,
Serum 25-hydroxyvitamin D level, and
Albumin levels
o Depression evaluation                                                                                                 
 20 minutes
Includes:
Hamilton Rating Scale for Depression


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Conducted at each follow-up visit as well
Clinical Global Impression – Improvement
Conducted at each follow-up visit as well
o Function evaluation                                                                                                     25 
minutes
Includes:
World Health Organization Disability Assessment Schedule 2.0
(WHODAS2)
Short Physical Performance Battery (SPPB)
Measure of Everyday Cognition (ECog)
Self-report fatigability measures (Borg Rating Scales, Pittsburgh Fatigability 
scale, Multidimensional Fatigue Inventory)
o Cognitive evaluation                                                                                                    30 
minutes
Includes:
Logical Memory (WMS III) 
Stroop Color-Word Test
Trailmaking Test A & B
Wechsler Adult Intelligence Scale - Revised (WAIS-R) Digit Symbol test
o Side Effect evaluation                                                                                                    5 
minutes
Includes:
Treatment Emergent Signs and Symptoms scale
Conducted at each follow-up visit as well
Please attach copies, unless standard instruments are used
Off label and investigational use of drugs/devices
Choose from the following that will be applicable to your study 
   Drug
Select the number of drugs used in this study
2
Drug #1
Name of the drug 
Escitalopram 
Manufacturer and other information
Manufactured by Forest Laboratories and sold under the brand name Lexapro, escitalopram is an SSRI
medication approved by the US Food and Drug Administration for the treatment of major depression.
Approval Status
No IND is required


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Choose one of the following options
FDA conditions are met (see 'Rules')
Explain
Although the FDA has not ruled as such, we believe an IND is not required for this project as no patients
will be treated in this study without significant depressive symptomatology (i.e. Patients with frailty 
but without dysthymia or MDD will not be included in this study).
Drug #2
Name of the drug
Duloxetine 
Manufacturer and other information
Manufactured by Eli Lilly and sold under the brand name Cymbalta, duloxetine is an SNRI medication
approved by the US Food and Drug Administration for the treatment of major depression.
Approval Status
No IND is required
Choose one of the following options
FDA conditions are met (see 'Rules')
Explain
Although the FDA has not ruled as such, we believe an IND is not required for this project as no patients
will be treated in this study without significant depressive symptomatology (i.e. Patients with frailty but 
without dysthymia or MDD will not be included in this study).
Research Related Delay to Treatment
Will research procedures result in a delay to treatment?
No
Treatment to be provided at the end of the study
Patients will be followed for one year in this study, and provided 3 months of subsequent
treatment at no cost to them, or if patients prefer, patients will be provided referral information for
further psychiatric follow up elsewhere.
Clinical Treatment Alternatives
Clinical treatment alternatives
Patients do not have to participate in this study to receive treatment for their depressive
symptoms. Many other available antidepressant medications have also been shown to be
effective in the treatment of depressive symptoms. In addition, some patients with similar
symptoms may respond to psychotherapy.


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Risks/Discomforts/Inconveniences 
Risks that could be encountered during the study period
The main risks in this study are the side effects of the medication. Commonly observed
side effects associated with escitalopram and duloxetine are diaphoresis, diarrhea, nausea,
insomnia, somnolence, disorder of ejaculation, impotence, and fatigue. Long-term use of
duloxetine is associated with the risk of worsening osteoporosis/osteopenia. The FDA black box
warning in the package insert for all SSRIs warning of increased suicidal ideation and behavior
does not apply to the age of patients included in this study. 
 
If patients require medications for sleep disturbance during the course of their participation, they 
will be prescribed lorazepam (up to 2 mg daily) or its equivalent, zolpidem (up to 10 mg), or trazodone (up 
to 150 mg). These medications have been used to successfully treat sleep disturbances. It is possible that 
patients may experience side effects from these medications. The side effects most commonly associated 
with lorazepam include sedation, somnolence, and falls. The side effects most commonly associated with 
zolpidem include fatigue and drowsiness, along with headache or muscle aches. The side effects most 
commonly associated with trazodone include dizziness, drowsiness, headache, and nausea.
 
Other potential risks that could be encountered include (1), during the assessment
procedures, some patients may find some questions upsetting, and (2), in the obtaining a 20 cc
blood sample, patients can experience side effects that include pain, fainting, bruising, lightheadedness,
and, on rare occasions, infection.
Describe procedures for minimizing risks
Side effects of the medications will be assessed at each follow-up assessment, with
emphasis on the assessment of mobility-related changes. If the side effects represent an
intolerable burden in the assessment of the patient or the treating clinician, the medication will be
discontinued.
 
Regarding the risks during the assessment procedures, if patients become upset during
the assessment of their cognition or functioning, they are not obliged to answer the questions; if
they wish to discontinue participation in the treatment protocol, they can withdraw their
participation at anytime without effecting their participation in any other study protocol. Regarding
the risk associated with blood draw, the staff will take every precaution to avoid these difficulties.
The staff members are all certified at the hospital to be drawing blood from patients, and are
instructed to keep the comfort and welfare of our patients as their primary priority.
Methods to Protect Confidentiality
Describe methods to protect confidentiality
The information obtained from this protocol will be kept strictly confidential and used for
professional purposes only. Each person participating in the study receives a coded number and


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only the researchers have access to the master list identifying names and numbers. All
electronically stored and transmitted data will use these code numbers only, and not names or
other identifying information. Only research staff and institutional personnel will review the
records. Publications using this data will be done in a manner that fully protects the subject’s
anonymity.
Will the study be conducted under a certificate of confidentiality?
No
Direct Benefits to Subjects  
Direct Benefits to Subjects
Patients who are not currently in treatment and are experiencing depressive symptoms may
receive a medication effective for improving their depressive symptoms. Therefore, the major benefit is that 
patients may achieve treatment response from their depressive symptomatology as a result of participating 
in the study.
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
Participants will not be compensated, however, they will be reimbursed for travel expenses up to $10 per 
visit. They will not have to pay for any of the study medications, medical examinations, or laboratory tests 
that are required for this study. 
References
References
Binder EF, Yarasheski KE, Steger-May K, et al. Effects of progressive resistance training on body
composition in frail oder adults: Results of a randomized, controlled trial. J Gerontol Med Sci.
2005; 60A: 1425-1431.
 
Brown M, Sinacore DR, Binder EF, Kohrt WM. Physical and performance measures for the
identification of mild to moderate frailty. J Gerontol Med Sci. 2000; 55A: 350–355.
 
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J
Gerontol A Biol Sci Med Sci. 2001; 56(3): 146-156.


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Uploads
Upload the entire grant application(s)
Upload copy(ies) of unbolded Consent Form(s)
Upload copy(ies) of bolded Consent Form(s)
Upload copy(ies) of recruitment materials/ads to be reviewed
Upload copy(ies) of the HIPAA form
Frailty_HIPAA_4-18 unstamped unchanged.pdf
Upload any additional documents that may be related to this study
7289R Data Request for Use of De-Identified Data.pdf