Conditions: Sleep-Related Eating Disorder
Keywords: Sleep-Related Eating Disorder Topiramate Parasomnia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 34
Healthy volunteers: no

Brief summary:
The purpose of the study is to learn about the safety and effectiveness of oral (taken by mouth) topiramate in treating Sleep-Related Eating Disorder (SRED).

Detailed description:
This is a single center, 13-week, outpatient, randomized, double-blind, placebo-controlled, parallel group, pilot study of topiramate in subjects with Sleep-Related Eating Disorder (SRED). The primary objective of this study is to investigate the efficacy and safety of topiramate compared to placebo in the treatment of Sleep-Related Eating Disorder. SRED is a disorder that consists of out of control eating during the night with little or no awareness of the events. In this study we are comparing topiramate to placebo. A placebo is a pill that looks exactly like the study drug, but it does not have any active drug in it. Topamax (topiramate) is approved by the U.S. Food and Drug Administration (FDA) as a therapy for epilepsy, but topiramate has not been approved by the FDA for SRED.

Arms:
arm 1: Study medication arm, 25-300mg of Topiramate arm 2: Placebo arm of study, 25-300mg of sugar pill

Interventions: intervention 1: Topiramate or Placebo
Intervention descriptions: intervention 1: 25-300 mg tablets of topiramate and matching placebo, placed in blinded capsules

Protocol document:
Prot_SAP_000.pdf: 
 
 
1 
 
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to 
Determine the Efficacy and Safety of Topiramate in the Treatment of Sleep-
Related Eating Disorder (SRED) 
 
Principal Investigator: John W. Winkelman, MD PhD 
Detailed Protocol 
Version Date: 6/8/2016 
 
Background and Significance 
 
Sleep-Related Eating Disorder (SRED) is a parasomnia characterized by arousals from sleep, 
compulsive consumption of food, poor sleep quality, and morning anorexia. SRED is generally 
more prevalent in females, with onset in early adulthood. SRED is thought to be closely related 
to Night Eating Syndrome (NES), another night-time eating disorder. It is thought that SRED 
and NES are related processes in which night-time eating occurs along a variable spectrum of 
arousal; individuals with NES are fully conscious during their night-eating episodes, whereas 
individuals with SRED are only partially conscious during their night-eating episodes1.  This 
nosology is reflected in the most recent diagnostic criteria for SRED in the International 
Classification of Sleep Disorders, Second Edition (ICSD-2) in which the level of consciousness 
is not a diagnostic criteria, stressing rather, that the sleep-related eating behavior is involuntary 
in nature.    
 
Night Eating Syndrome was first reported in 19552, however the syndrome was not further 
investigated and defined until almost 30 years later, and still lacks standard diagnostic criteria. 
Its prevalence in the general population is uncommon, estimated at 1.5%, but more common in 
the severely obese population, with estimates ranging from 9 to 43%3. Onset of the syndrome 
has been linked to stressful life experiences. Individuals with NES experience morning anorexia, 
consume over half of their daily caloric intake after 6 PM and suffer from insomnia4. NES 
patients have full awareness of their night-eating episodes; however, the binge eating is 
compulsive and difficult to suppress5.  
 
Sleep-Related Eating Disorder has only been reported in the last decade. It has been estimated 
that approximately 1% of young adults have exhibited this behavior, which usually occurs 
nightly, sometimes several times a night. Patients with SRED may have variable level of 
awareness during an episode of night eating, often describing their eating occurring while they 
are “half awake” or “half asleep”. Amnesia may be present the morning after an episode, and 
thus the occurrence of such an episode must be inferred from evidence observed in the 
morning. Individuals tend to eat high calorie foods, and some consume inappropriate foods (e.g. 
frozen foods, non-nutritive substances) during episodes. Weight gain is often associated with 
this behavior. Sleep disorders such as Restless Legs Syndrome and somnambulism are 
common among these patients. 
 
Current treatments for SRED have been directed towards treating any underlying sleep 
disorder, eating or psychiatric disorder. Selective serotonin reuptake inhibitors (SSRIs), 
dopaminergic agonists, benzodiazepines, anorectics, hypnotics and opioids have been used, 
but success in treatment has varied.  
 
 
 
 


 
 
2 
 
Preliminary Reports with Topiramate 
 
Preliminary reports of topiramate in individuals with NES or SRED indicate that topiramate may 
be a beneficial in the treatment of these syndromes. In an open-label study of four subjects (two 
with NES, two with SRED), one subject had complete elimination of night eating (NES subject), 
two had a 75-<100% reduction in night eating, and one had a 50-<75% reduction in night 
eating5. The dose of topiramate ranged from 100 mg-400 mg daily, with an average dose of 216 
mg. Subjects also experienced weight loss ranging from 15-33 pounds. Topiramate was well 
tolerated. In addition to this study, a case study of a patient with NES and co-morbid Post-
traumatic Stress Disorder reported improvement of NES with topiramate treatment7. More 
recently, there have been two larger case series published examining the use of topiramate in 
SRED8,9. In the case series of 17 patients conducted by Schenck and Mahowald, topiramate 
fully/substantially controlled in all 11 subjects who were able to continue with topiramate therapy 
[6 subjects discontinued the medication; 4 due to lack of efficacy and 2 due to side effects 
(purtiris, weight gain)]8. In the retrospective case series conducted by Winkelman, over two-
thirds (17/35) patients treated with topiramate were considered responders9. These reports 
suggest that further investigation of topiramate as a potential treatment for SRED is warranted.  
 
Topiramate Background 
 
Topiramate is a sulfamate-substituted monosaccharide derived from fructose. It is structurally 
distinct from any other anti-epileptic medication10. Topiramate is a structurally novel compound 
that is an effective anticonvulsant with a good safety profile after oral administration in animals 
and humans. Topiramate has been approved for marketing in the United States and most 
European Union countries for adjunctive treatment of pediatric and adult patients with partial 
onset seizures, Lennox-Gastaut syndrome, or primary generalized tonic-clonic seizures. It has 
also been approved as monotherapy in some countries. Topiramate is currently under 
investigation for a number of other disorders including migraine, bipolar disorder, and essential 
tremor. For a complete profile, see the package insert11. 
 
Nonclinical Studies 
 
Pharmacologic Profile11 
Topiramate has multiple mechanisms of action that may contribute to its anti-convulsant 
properties, as well as its potential therapeutic effect in other Central Nervous System (CNS) 
disorders. First, the drug inhibits voltage gated sodium channels and thus suppresses action 
potentials associated with sustained repetitive cell firing. Second, topiramate augments the 
inhibitory chloride ion influx mediated by g-aminobutyrate (GABA). This is not blocked by 
flumazenil suggesting that the mechanism is different from that of benzodiazepines. Third, 
topiramate antagonizes the (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) 
AMPA/kainate subtype of the glutamate receptor. It has no effect on the N-methyl-D-aspartate 
(NMDA) subtype. Fourth, topiramate reduces the firing of high voltage-activated (L-type) 
calcium channels. It is also a weak inhibitor of some isoenzymes of carbonic anhydrase. 
 
Toxicology 
The data for preclinical toxicology studies were obtained for dosage levels up to the maximum 
tolerated doses. Female rats and male and female dogs have received higher systemic 
exposure to topiramate than the highest anticipated clinical exposure in humans. It is notable 
that the female rat appears to provide the best animal model for human metabolism of 
topiramate. 
 


 
 
3 
 
In general, acute and long-term oral exposure of mice, rats, dogs, and rabbits to topiramate was 
well tolerated. Hyperplasia of the gastric and urothelial cells seen in shorter term studies did not 
progress to neoplasia after lifetime exposure in rats or mice and has not been reported during 
clinical studies. Smooth muscle tumors of the urinary bladder in mice appear to be unique to the 
species. There is no known clinical counterpart; therefore, these tumors were not considered to 
be of relevance to man. As with many other anticonvulsants, topiramate is teratogenic in mice, 
rats and rabbits. The teratologic effects of topiramate seen in rats and rabbits appear to be 
related to carbonic anhydrase inhibition. Reductions in weight of progeny were also indicated by 
reproductive studies in these species, but no effects on fertility were observed for male or 
female rats. Based on results of in vitro and in vivo mutagenicity assays, topiramate does not 
show genotoxic potential. For further background on the toxicology of topiramate, see the 
Investigator’s Brochure.10 
 
Pharmacokinetic Profile 
Studies in humans show that topiramate is rapidly absorbed, with peak concentrations occurring 
at approximately 2 hours following an oral dose. The bioavailability of topiramate from tablet 
formulation is approximately 80% compared to a solution. Bioavailability is not affected by food. 
Topiramate exhibits linear pharmacokinetics with dose proportional increases in plasma 
concentration over the 100-400 mg b.i.d. (200-800 mg/day) dose range studied. Topiramate is 
poorly bound to plasma proteins, 13-17% (over the concentration range of 1-250 mcg/ml), but 
there is a low-capacity erythrocyte binding site for the drug. The mean plasma elimination half-
life is 21 hours after single or multiple doses. Steady state is reached in approximately 4 days in 
subjects with normal renal functioning. The major route of elimination is via the kidneys. 
 
Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine 
(approximately 70% of an administered dose). Six metabolites have been identified, none of 
which constitutes more than 5% of an administered dose. The metabolites are formed via 
hydroxylation, hydrolysis, and glucuronidation. Overall, plasma clearance is approximately 20 to 
30 mL/min in humans following oral administration. Evidence of renal tubular reabsorption of 
topiramate was demonstrated in rats given probenecid to inhibit tubular reabsorption along with 
topiramate, where a significant increase in renal clearance of topiramate was observed. 
 
OBJECTIVE 
 
The primary objective of this study is to investigate the efficacy and safety of topiramate 
compared to placebo in the treatment of Sleep-Related Eating Disorder. 
 
OVERVIEW OF STUDY DESIGN 
 
This is a single center, 13-week, outpatient, randomized, double-blind, placebo-controlled, 
parallel group, pilot study of topiramate in subjects with Sleep-Related Eating Disorder.  
After giving informed consent, subjects who meet all the inclusion and exclusion criteria may be 
enrolled. The study will consist of two phases: 
 
• 
pre-randomization phase (up to 56 days prior to randomization), consisting of a 
screening/washout period (up to 42 days) and a prospective baseline period (14 days); 
• 
treatment phase, consisting of titration period: up to 9 weeks; maintenance period: 4 weeks; 
taper period: 2 weeks. 
 


 
 
4 
 
The study medication will be titrated to 300 mg/day or the subject’s minimum effective dose. 
Subjects must reach a minimum dose of 25 mg/day after the second week of titration. The taper 
period will last approximately two weeks during which subjects will gradually reduce their 
medication until they are no longer taking the study medication. 
 
SUBJECT POPULATION 
 
General Considerations 
This study will enroll up to 240 subjects with the goal of randomizing 40 subjects with Sleep-
Related Eating Disorder. The specific inclusion and exclusion criteria for enrolling subjects in 
this protocol are outlined below. Our estimated completion date for the study is January 2015.  
 
Inclusion Criteria 
Subjects must satisfy the following criteria before entering the study:  
 
1. Subjects must have a diagnosis of the following for at least 6 months: 
 
Sleep-Related Eating Disorder, defined as (according to ISCD-2 criteria): 
 
A. Recurrent episodes of involuntary eating and drinking occur during the main sleep 
period.  
B. One or more of the following must be present with the recurrent episodes of involuntary 
eating and drinking: 
i. Consumption of peculiar forms or combinations of food or inedible or toxic 
substances 
ii. Insomnia related to sleep disruption from repeated episodes of eating, 
with a complaint of nonrestorative sleep, daytime fatigue, or somnolence 
iii. Sleep related injury 
iv. Dangerous behaviors performed while in pursuit of food or while cooking 
food 
v. Morning anorexia 
vi. Adverse health consequences from recurrent binge eating of high-caloric 
foods 
C. The disturbance is not better explained by another sleep disorder, medical or neurologic 
disorder, mental disorder, medication use, or substance use disorder 
 
2. Subjects must experience 3 nights per week of nocturnal eating during the 14-day 
prospective baseline period prior to Visit 2.  
 
3. Subjects must be between 18 and 75 years of age. 
 
4. Subjects must be able to take oral medication in capsule form, adhere to medication regimens 
and be willing to return for regular visits. 
 
5. Subjects must have observed the designated washout periods for prohibited medications 
outlined under the Concomitant Therapy section of this protocol. 
 
6. Female subjects must be: 
• 
postmenopausal for at least one year, surgically sterile, or 
• 
practicing an effective method of birth control (e.g., contraceptive injections, intrauterine 
device, double-barrier method, contraceptive patch, male partner sterilization, abstinence 


 
 
5 
 
and agree to continue abstinence or to use an acceptable method of contraception, as 
listed above, should sexual activity commence) before entry and throughout the study 
• 
If taking prescription oral contraceptives, must agree to also use a barrier method of birth 
control throughout the study since topiramate may affect the metabolism of prescription oral 
contraceptives.  
• 
Have a negative urine pregnancy test at Visit 2 (Day 1). 
 
7. Subjects must be able to read and comprehend written instructions, and be willing and able to 
comply with protocol requirements. 
 
8. Subjects must have signed an informed consent document indicating that they understand 
the purpose of and procedures required for the study and are willing to participate in the 
study 
 
Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following criteria: 
 
1. Subjects with evidence of untreated primary sleep disorders (e.g.,Obstructive Sleep Apnea, 
Restless Legs Syndrome, Periodic Leg Movements of Sleep) as determined in the sleep 
screening questionnaire and clinical history.   
 
2. Subjects who have a DSM-IV diagnosis of substance dependence or abuse (with the 
exception of nicotine) that has been active within the past 6 months. 
 
3. Subjects taking exclusionary medications, such as benzodiazepines/benzodiazepine 
receptor agonists, tricyclic antidepressant medications or antipsychotics as these 
medications have been reported to cause SRED12-15, who are unable or unwilling to 
complete the required washout of these medications. 
 
4. Subjects with an active or unstable major psychiatric disorder requiring further treatment 
(e.g., major depressive disorder). Subjects with clinically significant depression defined by a 
HAM-D >20 or who, in the investigator’s judgment might require intervention with either 
pharmacological or non-pharmacological therapy over the course of the study, will also be 
excluded. 
 
5. Subjects with an active daytime DSM-IV-TRä diagnosis of Anorexia Nervosa or Bulimia 
Nervosa within the 3 months prior to screening. 
 
6. Subjects judged clinically to be at serious suicidal or homicidal risk. 
 
7. Subjects with a body mass index (BMI) ³50 kg/m2. 
 
8. Subjects who have positive urine drug screening (phencyclidine, cocaine, amphetamines, 
tetrahydrocannabinol, and opiates) at Visit 1 (Day -14). 
 
9. Subjects who report consumption of more than 2 alcoholic beverages daily, 14 or more 
alcoholic beverages weekly 
 
10. Subjects who report consumption of more than 4 beverages containing caffeine daily. 
 


 
 
6 
 
11. Subjects who are rotating or third shift workers. 
 
12. Subjects who are pregnant or lactating. 
 
13. Subjects with a history of recurrent nephrolithiasis or on another carbonic anhydrase 
inhibitor. 
 
14. Subjects with progressive or degenerative neurological disorders or a structural disorder of 
the brain from birth, trauma or past infection. 
 
15. Subjects who have recently had or are planning to have surgery. 
 
16. Subjects who have previously been treated with topiramate and discontinued treatment due 
to an adverse event or subjects with a known hypersensitivity to topiramate. 
 
17. Subjects who have previously taken Topiramate. 
 
 
18. Subjects known to have clinically significant, unstable medical conditions as determined by 
careful clinical interview and review of medical records, including but not limited to:  
• 
Symptomatic coronary artery disease or peripheral vascular disease  
• 
Malignancy or history of malignancy within the past 5 years (except basal cell 
carcinoma) 
• 
Clinically significant renal disease including creatinine >1.5 or creatinine clearance 
(calculated by standard method) <60 
• 
Clinically significant diseases of the gastrointestinal system including active liver disease 
with a history of LFTs >3x ULN as determined by review of medical history or records 
• 
Any disease or condition that compromises the function of those body systems that 
could result in altered absorption, excess accumulation, or impaired metabolism or 
excretion of topiramate 
19. Subjects who have participated in an investigational drug or device trial within the 4 weeks 
prior to enrollment. 
 
20. Subjects who in the opinion of the investigator should not be enrolled in the study because 
of the Precautions, Warnings or Contraindications sections of the topiramate package insert. 
 
21. Subjects with glaucoma. 
 


 
 
7 
 
STUDY MEDICATION AND SUPPLIES 
 
Study Treatments 
The study medication will consist of 25 mg or 100 mg of topiramate tablets, or matching 
placebo, prepared in identically appearing capsules by the MGH IDS. The medication will be 
titrated over a 9-week period according to the following suggested schedule: 
 
Titration Schedule * 
Double-Blind Topiramate / Placebo Dosing 
Days 
Study Medication 
Total Daily Dose 
25 mg Tablets 
100 mg Tablets 
Topiramate 
Placebo 
1-7 
1 capsule  
 
25 mg 
Matching 
capsules 
8-14 
2 capsules 
 
50 mg 
15-21 
3 capsules  
 
75 mg 
22-28 
4 capsules 
 
100 mg 
29-35 
5 capsules 
 
125 mg 
36-42 
6 capsules 
 
150mg 
43-49 
 
2 capsules 
200mg 
50-56 
2 capsules 
2 capsules 
250 mg 
57+ 
 
3 capsules 
300 mg 
 
Subjects will be instructed to take the study medication one hour prior to bedtime (h.s.). 
Subjects will be informed during the consent process that they may be asked to take up to six 
pills at different points during the titration period.  The study medication will be titrated to 300 
mg/day or the subject’s minimum effective dose (MED).  
 
At the investigator’s discretion the titration rate may be adjusted. However, after the second 
week of titration, subjects must take at least 25 mg/day of topiramate or matching placebo for 
the duration of the double-blind phase. During the maintenance period, subjects should remain 
at the dose attained at the end of the titration period, however dose adjustments will be 
permitted at the discretion of the investigators.  
 
Subjects will taper their study medication by decreasing the dose by approximately 30% every 
three days over approximately a 14-day period until they are no longer taking study medication. 
 
*Subjects with an estimated creatinine clearance <70 but >60 will be included in the study, but 
will follow a modified titration schedule. Dose increases for these subjects will be take place no 
less than every 14 days rather than every 7 days, and at the end of the titration period they will 
reach a maximum dose of 125mg. During the maintenance period, subjects should remain at 
the dose attained at the end of the titration period, however dose adjustments will be permitted 
at the discretion of the investigators up to a maximum dose of 150mg.  
 
Study Medication Packaging 
Medication will be prepared and packaged by the MGH IDS Pharmacy. For the first 6 weeks of 
the titration period the investigator will dispense bottles with sufficient 25mg capsules for 7+3 
days of the necessary dose. After the subject reaches a dose of 150 mg the medications will be 
packaged in bottles as prescribed by the investigator depending on the dose and number of 
tablets needed. All study medication will be dispensed in child-resistant packaging. Bottles will 
be labeled with the patient name and ID and the dosing information. Bottles will be clearly 
labeled as containing either 25 mg or 100 mg matching placebo or topiramate tablets. 


 
 
8 
 
Subjects will be dispensed the appropriate number of tablets needed until they return for their 
next office visit. Study medication should be stored at room temperature 15-30°C (59-86°F), be 
protected from moisture, and be maintained in a secure area. 
 
Study Medication Accountability and Compliance 
Starting at Visit 2 (Day 1), study medication will be dispensed to each subject with instructions 
to return all unused medication and packaging (including empty bottles) at the next study visit in 
order to assess compliance. Returned study medication bottles may be redispensed to the 
same subject if appropriate. Additional bottles will be dispensed to each subject as needed. 
 
All study medication dispensed by the investigator or designee will be accounted for throughout 
the study. Information about subject dosing and compliance will be recorded in the subject’s 
study records.  
 
Subjects who are noncompliant with medications (according to pill counts and diaries) may  be 
removed from the study at the discretion of the investigators.  
 
The investigator agrees not to allow access to the study medication to any person except those 
named as sub-investigator(s) or clinical care staff, and dispense only to qualified subjects 
participating in the study.  
 
Randomization  
Randomization will be used to avoid bias in the assignment of subjects to treatment, to increase 
the likelihood that known and unknown subject attributes (e.g., demographics and baseline 
characteristics) are evenly balanced across treatment groups, and to enhance the validity of 
statistical comparisons across treatment groups. Blinded treatment will be used to reduce 
potential bias during data collection and evaluation of clinical endpoints. 
 
At the time of Screening (Visit 1A), subjects will be assigned a three-digit subject number, in 
ascending sequential order beginning with 001. The subject number will be retained by the 
subject for the duration of the study. The MGH IDS Pharmacy will provide and maintain 
randomization and blinding. Subjects will be randomized to receive either topiramate or placebo 
in a 1:1 ratio. The randomization will be balanced by using permuted blocks of 4. Subject and 
investigator will be blinded to treatment assignment. Subjects will be randomized sequentially as 
they qualify for the study. 
 
Blinding 
The randomization code will be maintained by the MGH IDS Pharmacy and will not be revealed to 
study subjects, investigators or clinical staff until all subjects have completed and the database has 
been finalized. 
 
To maintain the blind, sealed envelopes containing the study drug identification (e.g., active or 
placebo) will be provided to the investigator. These sealed envelopes will be kept together, in a 
limited access area that is accessible 24 hours per day. The study drugs will be identical in 
appearance and will be packaged in identical containers. 
 
Under normal circumstances, the blind should not be broken. The blind should be broken only if 
specific treatment would be dictated by knowing the treatment status of the subject.. Individual 
code breaks by the investigator will normally result in withdrawal of the subject from the trial. 
The date, time and reason for the unblinding must be documented in the study files.  


 
 
9 
 
After the termination of the double-blind portion of the study, subjects can be made 
aware of the study medication they were given at their request.  
 
Medication Side Effects 
The package insert for Topamax includes warnings and precautions related to the following side 
effects or adverse events: acute myopia and secondary angle closure glaucoma, oligohidrosis, 
psychomotor slowing, difficulty with concentration, speech or language problems (word-finding 
difficulties in particular), somnolence, fatigue, kidney stones, paresthesia, dizziness, ataxia, 
difficulty with memory, and diplopia. Dose-related adverse events at doses greater than 200mg 
per day also include nervousness, confusion, depression, anxiety, anorexia, and weight loss. 
 
 
STUDY EVALUATIONS 
 
General Considerations 
Starting at Visit 1, subjects will be required to keep a daily sleep and eating diary for the 
duration of the study. The following information will be collected: bedtime, time to fall asleep, 
whether the subject awoke during the night to eat, number of times the subject awoke to eat, 
duration and level of consciousness of each awakening, whether the subject remembers all of 
his/her night eating episodes, final wake time and time spent asleep. The diary will also capture 
the number of tablets of study medication taken. In addition, the diary includes an optional 
section for a bed partner or family member to provide information about witnessed night eating 
events. 
 
Assessment scales included in this protocol will be administered/completed as outlined in the 
visit schedule. Evaluations for each phase of the study will be performed as described below. 
 
Once a subject is randomized and is taking the study drug capsules, all visits must occur within 
a window of +/- 3 days of the schedule as given below. 
 
Pre-randomization Phase 
The Pre-randomization Phase may last up to 42 days based on washout requirements, not 
including a 14-day prospective baseline period. At Visit 1A (up to Day -42), the study will be 
explained and subjects will provide informed consent to participate in the study. Subjects will 
complete Visit 1 (Day -14) screening procedures following appropriate washout of prohibited 
medications. 
 
Visit 1A* (Up to Day -56) 
1. Obtain informed consent  
2. Review inclusion/exclusion criteria  
3. Assess previous and concomitant medications. Medication used for the past 42 days must 
be obtained.  
4. Obtain detailed medical and psychiatric history and permission to contact primary care 
provider(s) for medical records 
5. Perform physical examination 
6. Perform neurological examination 
7. Administer the eating disorders portion of the SCID 
8. Obtain height and weight 
9. Administer Hamilton Rating Scale for Depression (HAM-D) 
10. Administer the Eating Attitudes Test 
11. Schedule return visit 


 
 
10 
 
 
Visit 1* (Day -14) 
1. Review inclusion/exclusion criteria  
2. Assess concomitant medications  
3. Obtain weight 
4. Obtain non-fasting clinical laboratory tests as follows: 
- 
Urine Drug Screen [cocaine, amphetamines, methamphetamines, benzodiazepines, 
tetrahydrocannabinol (THC), and opiates]. 
- 
Hemoglobin A1C 
- 
Creatinine (creatinine clearance will be calculated using standard formula) 
5.   Perform urine pregnancy test (subjects of childbearing potential only) 
6.   Administer the Three Factor Eating Questionnaire (TFEQ) 
7.   Administer the Sheehan Disability Scale 
8.   Dispense sleep and night eating diary 
9.   Record adverse events 
10. Schedule return visit 
 
*Visits 1A and 1 may be combined for subjects who do not require washout from prohibited 
medications. 
 
Subjects who are eligible for study entry based on the results of the above will be instructed to 
return for Visit 2 (Day 1). 
 
 
Double-Blind Phase 
Subjects who continue to meet all entrance criteria will be randomized for study entry at Visit 2 
(Day 1). The following procedures will be performed: 
 
Visit 2 (Day 1) 
1. Review inclusion/exclusion criteria  
2. Assess concomitant medications  
3. Administer the Medical Outcome Study (MOS) Sleep Scale 
4. Administer the Epworth Sleepiness Scale  
5. Collect and review sleep and night eating diary  
6. Dispense sleep and night eating diary 
7. Record adverse events  
8. Dispense study medication 
9. Schedule return visit in one week 
 
Visit 3 (Day 7) 
1. Assess concomitant medications  
2. Obtain weight 
3. Collect and review sleep and night eating diary 
4. Dispense sleep and night eating diary 
5. Collect study medication and perform drug accountability 
6. Record adverse events 
7. Dispense study medication 
8. Schedule phone contact in one week and return visit in two weeks 


 
 
11 
 
 
Telephone contact (Day 14) 
1. Assess concomitant medications  
2. Discuss sleep and eating diary and remind subject to complete diary daily 
3. Discuss medication compliance and remind subject to take medication daily 
4. Record adverse events 
5. Discuss medication dose and make adjustments if indicated 
6. Offer option to come in to clinic for unscheduled visit in the event that subject wishes to 
discuss adverse events or issues with study protocol and compliance 
7. Confirm scheduled return visit in one week 
 
Visit 4 (Day 21) 
1. Assess concomitant medications  
2. Obtain weight 
3. Collect and review sleep and night eating diary 
4. Dispense sleep and night eating diary 
5. Collect study medication and perform drug accountability 
6. Record adverse events 
7. Dispense study medication 
8. Schedule phone contact in one week and return visit in two weeks 
 
Telephone Contact (Day 28) 
1.   Assess concomitant medications  
2.   Discuss sleep and eating diary and remind subject to complete diary daily 
3.   Discuss medication compliance and remind subject to take medication daily 
4.   Record adverse events 
5.   Discuss medication dose and make adjustments if indicated 
6.   Offer option to come in to clinic for unscheduled visit in the event that subject wishes to 
      discuss adverse events or issues with study protocol and compliance 
7.   Confirm scheduled return visit in one week 
 
Visit 5 (Day 35) 
1. Assess concomitant medications  
2. Obtain weight 
3. Perform urine pregnancy test (subjects of childbearing potential only) 
4. Administer the Medical Outcome Study (MOS) Sleep Scale 
5. Administer the Epworth Sleepiness Scale  
6. Administer the HAM-D 
7. Collect and review sleep and night eating diary 
8. Dispense sleep and night eating diary 
9. Collect study medication and perform drug accountability 
10. Record adverse events 
11. Dispense study medication 
12. Schedule phone contact in one week and return visit in two weeks 
 
Telephone Contact (Day 42) 
1.   Assess concomitant medications  
2.   Discuss sleep and eating diary and remind subject to complete diary daily 
3.   Discuss medication compliance and remind subject to take medication daily 
4.   Record adverse events 
5.   Discuss medication dose and make adjustments if indicated 


 
 
12 
 
6.   Offer option to come in to clinic for unscheduled visit in the event that subject wishes to 
      discuss adverse events or issues with study protocol and compliance 
7.   Confirm scheduled return visit in one week 
 
Visit 6 (Day 49) 
1.  Assess concomitant medications  
2.  Obtain weight 
3. Collect and review sleep and night eating diary 
4. Dispense sleep and night eating diary 
5. Collect study medication and perform drug accountability 
6.  Record adverse events 
7.  Dispense study medication 
8. Schedule phone contact in one week and return visit in two weeks 
 
 
Telephone Contact (Day 56) 
1.   Assess concomitant medications  
2.   Discuss sleep and eating diary and remind subject to complete diary daily 
3.   Discuss medication compliance and remind subject to take medication daily 
4.   Record adverse events 
5.   Discuss medication dose and make adjustments if indicated 
6.   Offer option to come in to clinic for unscheduled visit in the event that subject wishes to 
      discuss adverse events or issues with study protocol and compliance 
7.   Confirm scheduled return visit in one week 
 
Visit 7 (Day 63)  
1. Assess concomitant medications  
2. Obtain vital signs (sitting blood pressure, pulse, and weight) 
3. Perform urine pregnancy test (subjects of childbearing potential only) 
4. Administer the Medical Outcome Study (MOS) Sleep Scale 
5. Administer the Epworth Sleepiness Scale  
6. Collect and review sleep and night eating diary 
7. Dispense sleep and night eating diary 
8. Collect study medication and perform drug accountability 
9. Record adverse events 
10. Dispense study medication 
11. Schedule return visit in four weeks 
 
Telephone Contact (Day 77) 
1. Assess concomitant medications 
2. Record adverse events 
3. Confirm return visit in two weeks 
 
Visit 8 (Day 91)  
1. Assess concomitant medications  
2. Perform physical examination 
3. Obtain weight 
4. Administer the Medical Outcome Study (MOS) Sleep Scale 
5. Administer the Epworth Sleepiness Scale  
6. Administer the HAM-D 
7. Administer the TFEQ 


 
 
13 
 
8. Administer the SDS 
9. Obtain blood sample for HbA1C 
10. Collect and review sleep and night eating diary 
11. Collect study medication and perform drug accountability 
12. Record adverse events 
13. Dispense medication and instruct the subject on tapering.  
14. Schedule Post-Taper Visit 9 (Day 105) in approximately 2 weeks 
 
Taper Period  
After completion of the titration and maintenance periods (13 weeks), subjects will taper their 
study medication by decreasing their dose by approximately 30% every three days. Subjects will 
return for Visit 9 (Day 105) and the following procedures will be performed: 
 
Visit 9 (Day 105) 
1. Assess concomitant medications 
2. Obtain weight 
3. Record adverse events 
4. Collect study medication and perform drug accountability 
 
Early Withdrawal 
Subject participation may be terminated based upon subject choice, protocol violation (e.g., 
non-compliance), adverse event, or if a subject is lost to follow-up. The primary reason for 
withdrawal should be clearly indicated in the subject’s study file. 
 
In the event that a subject discontinues prematurely, final visit procedures will be performed at 
the time of discontinuation, if possible. Subjects who discontinue prematurely should be 
scheduled promptly for final visit (Visit 8, Day 91) procedures, preferably within 24 hours of the 
last dose. Subjects should taper study medication as discussed under Study Treatments. All 
adverse events should be followed to resolution, if possible. All unused study medication must 
be returned to the investigator. 
 
CONCOMITANT THERAPY 
 
General 
Subjects may have concurrent illnesses that require prescription or over-the-counter medication 
during the course of the study. All exclusionary medications taken within 4 weeks (28 days) prior to 
Visit 1 (Day-14), with the exception of flurazepam and protriptyline which should be recorded within 
5 weeks (35 days) and 6 weeks (42 days), respectively, of Visit 1, as well as those continued at the 
start of the study or started during the study (other than study medication), including the drug 
name, dose, duration and indication for use, should be recorded in the subjects’ study files. 
 
If the patient is taking a prohibited medication, the investigator and patient will discuss the risk and 
benefits of a trial of tapering and discontinuation of the medication.  Any potential medication 
discontinuation will also be discussed with the prescribing physician.   
 
Modifications to a subject’s pre-existing treatment and regimen are not to be made for the explicit 
purpose of entering this trial, but should be done only where deemed clinically appropriate by the 
investigator. 
 
The following medications are prohibited during the trial and subjects must observe the 
designated washout periods prior to Visit 1 (Day -14): 


 
 
14 
 
 
 
 
 
Prohibited Medications Prior to Visit 1 (Day –14) 
and During the Trial 
Washout 
Period 
Anorexigenic agents for obesity management, including, but 
not limited to: 
• 
Sibutramine (MeridiaÒ) 
• 
Orlistat (AlliTM, XenicalÒ) 
• 
Over-the-counter agents such as phentermine, hypericum 
• 
Herbal preparations, including but not limited to: 
• 
Mah Wang 
• 
Ephedra 
• 
Herbal-life 
• 
Tahitian Noni-Juice 
4 weeks 
Tricyclic Antidepressants  
• 
imipramine (TofranilÒ) 
• 
reboxetine (EdronaxÒ) 
• 
trimipramine (SurmontilÒ) 
1 week 
• 
desipramine (NorpramineÒ) 
• 
amoxapine (AsendinÒ) 
• 
maprotiline 
• 
nortriptyline (PamelorÒ, AventylÒ) 
• 
clomipramine (AnafranilÒ) 
• 
amitriptyline (ElavilÒ) 
• 
doxepin (SinequanÒ) 
2 weeks 
• 
protriptyline (VivactilÒ) 
6 weeks 
 
Benzodiazepine Receptor Agonists 
       • zolpidem (AmbienÒ, Ambien CRÒ) 
         • eszopiclone (LunestaÒ) 
       • zopiclone (ImovaneÒ, ZimovaneÒ) 
       • zaleplon (SonataÒ) 
 
2 weeks 
 
  Benzodiazepines 
• 
estazolam (ProsomÒ) 
• 
lorazepam (AtivanÒ) 
• 
temazepam (RestorilÒ) 
• 
triazolam (HalcionÒ) 
 
1 week 
• 
alprazolam (XanaxÒ) 
 
2 weeks 
      ●     clonazepam (Klonopinâ) 
• 
clorazepate (TranxeneÒ) 
• 
quazepam (DoralÒ) 
 
3 weeks 
      ●     flurazepam (DalmaneÒ ) 
• 
chlordiazepoxide (Librium) 
 
5 weeks 
     Drugs with mixed actions 
        ●     mirtazapine (RemeronÒ) 
2 weeks 


 
 
15 
 
 
     MAO Inhibitors  
• 
isocarboxazid (MarplanÒ) 
• 
phenelzine (NardilÒ)  
4 weeks 
• 
tranylcypromine (ParnateÒ)  
• 
selegiline hydrochloride (EldeprylÒ)) 
5 weeks 
   Antiepileptic agents 
• 
topiramate (TopamaxÒ) 
• 
phenytoin sodium, phenytoin (Dilantinâ) 
• 
phenytoin sodium (PhenytekÔ)  
• 
methsuximide (Celontinâ) 
• 
valproate sodium (Depaconâ) 
• 
valproic acid (Depakeneâ) 
• 
divalproex sodium, divalproex, valproic acid (Depakoteâ) 
• 
ethosuximide (Zarontinâ) 
• 
carbamazepine (Tegretolâ, Carbatrolâ, EpitolÒ) 
 
3 weeks 
 
Dopamine antagonists 
• 
perphenazine (Trilfonâ) 
• 
thioridazine (Mellarilâ) 
• 
trifluoperazine (Stelazineâ) 
• 
fluphenazine (Prolixinâ, Permitilâ) 
 
3 weeks 
• 
mesoridazine (Serentiâl) 
• 
chlorpromazine (Thorazineâ) 
• 
haloperidol (Haldolâ) 
• 
droperidol (Inapsineâ) 
• 
thiothixene (Navaneâ) 
  
 
3 weeks 
Carbonic anhydrase inhibitors  
• 
acetazolamide (Diamoxâ) 
• 
triamterene (Dyazideâ, Dyreniumâ, Maxzideâ) 
●     zonisamide (Zonegranâ) 
4 weeks 
Atypical Antipsychotics 
• 
risperidone (Risperdalâ) 
• 
olanzapine (Zyprexaâ, Zyprexa Zydisâ) 
 4 weeks 
Use of an investigational drug or device 
 
4 weeks 
 
*Chronic use of antacids and the use of calcium supplements greater than the recommended 
daily dose are prohibited during the trial. 
 
 
ADVERSE EVENTS 
This study follows Partners Health Care guidelines regarding the definitions and reporting 
policies of adverse events. 
Definition: An adverse event is any untoward or unfavorable medical occurrence in a human 
subject, including any abnormal sign (for example, abnormal physical exam or laboratory 
finding), symptom, or disease, temporally associated with the subject’s participation in the 
research, whether or not considered related to the subject’s participation in the research 


 
 
16 
 
(modified from the definition of adverse events in the 1996 International Conference on 
Harmonization E-6 Guidelines for Good Clinical Practice). 
 
This includes any occurrence that is new in onset or aggravated in severity or frequency from 
the baseline condition, or abnormal results of diagnostic procedures including laboratory test 
abnormalities. Any such event is considered an adverse event if it meets any of the following 
conditions: 
• 
results in discontinuation from the study; 
• 
requires treatment or any other therapeutic intervention; 
• 
requires further diagnostic evaluation (excluding a repetition of the same procedure to 
confirm the abnormality); or 
• 
is associated with clinical signs or symptoms judged by the investigator to have a significant 
clinical impact. 
 
Adverse events may or not be related to the study medication or research procedures. Those 
that are considered related meet the criteria listed below and those that are unrelated are all 
others that do not. Adverse events may be serious or non-serious. Serious adverse events 
include those that meet the criteria listed below, and non-serious adverse events include all 
others. Adverse events may also be unexpected or expected. Unexpected adverse events meet 
the criteria listed below and expected adverse events are all others that do not. 
 
Serious Adverse Event 
A serious adverse event is any untoward medical occurrence that meets the above definition 
and any of the following conditions: 
• 
results in death;  
• 
is life threatening (places the subject at immediate risk of death from the event as it 
occurred);  
• 
requires inpatient hospitalization or prolongation of existing hospitalization;  
• 
results in a persistent or significant disability/incapacity;  
• 
results in a congenital anomaly/birth defect; or  
• 
any other adverse event that, based upon appropriate medical judgment, may jeopardize 
the subject’s health and may require medical or surgical intervention to prevent one of the 
outcomes listed above (examples of such events include allergic bronchospasm requiring 
intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that 
do not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse). 
Note: Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in other situations; for example, important medical events may not be 
immediately life-threatening or result in death or hospitalization, but may jeopardize the subject 
or may require intervention to prevent one of the outcomes listed in the definition above. 
 
Unexpected (Unlisted) Adverse Event 
• Any adverse event occurring in one or more subjects participating in a research 
protocol, the nature, severity, or frequency of which is not consistent with either: 
• the known or foreseeable risk of adverse events associated with the procedures 
involved in the research that are described in (a) the protocol-related documents, 
such as the IRB-approved research protocol, any applicable investigator brochure, 


 
 
17 
 
and the current IRB-approved informed consent document, and (b) other relevant 
sources of information, such as product labeling and package inserts; or  
• the expected natural progression of any underlying disease, disorder, or condition of 
the subject(s) experiencing the adverse event and the subject’s predisposing risk 
factor profile for the adverse event. 
Associated with the Use of the Drug 
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable or very likely by the definitions listed below: 
 
Attribution Definitions 
 
• 
Not related 
An adverse event which is not related to the use of the drug. 
 
• 
Doubtful 
An adverse event for which an alternative explanation is more likely, e.g., 
concomitant drug(s), concomitant disease(s), and/or the relationship in 
time suggests that a causal relationship is unlikely. 
 
• 
Possible 
There is a reasonable possibility that the adverse event, incident, 
experience or outcome may have been caused by the procedures 
involved in the research (modified from the definition of associated with 
use of the drug in FDA regulations at 21 CFR 312.32(a)). A reasonable 
possibility is defined as more likely than not related to the research 
procedures or, in other words, there is a > 50% likelihood of the event 
having been caused by the procedures involved in the research. 
 
• 
Probable 
An adverse event which might be due to the use of the drug. The 
relationship in time is suggestive (e.g., confirmed by dechallenge). An 
alternative explanation is less likely, e.g., concomitant drug(s), 
concomitant disease(s). 
 
• 
Very likely 
An adverse event which is listed as a possible adverse reaction and 
cannot be reasonably explained by an alternative explanation, e.g., 
concomitant drug(s), concomitant disease(s). The relationship in time is 
very suggestive (e.g., it is confirmed by dechallenge and rechallenge). 
 
 
All Adverse Events 
All adverse events that occur between the first study-related procedure and within 30 days of 
the last dose of study medication will be reported. Adverse events will be reported to the PHRC 
according to their guidelines. 
 
Subjects should report any adverse events voluntarily or in response to general, non-directed 
questioning (e.g., “How has your health been since the last visit?). For each adverse event 
reported by the subject, the investigator should obtain all the information required to complete 
documentation in the subject’s research file. 
 
All adverse events, regardless of seriousness, severity, or presumed relationship to study therapy, 
must be recorded using medical terminology in the subject’s study documents. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (e.g., cough, 


 
 
18 
 
runny nose, sneezing, sore throat, and head congestion should be reported as “upper respiratory 
infection”). The investigator must document his/her opinion concerning the relationship of the 
adverse event to study therapy. All measures required for adverse event management must be 
recorded in the source document. 
 
Pregnancies 
Pregnancies occurring during the study will be reported by the investigational staff within one 
working day of their knowledge of the event. Any subject who becomes pregnant during 
participation in this study will be promptly withdrawn from the study. Follow-up information 
regarding the outcome of the pregnancy and any postnatal sequelae in the infant will be  
required. 
 
Compensation 
Subjects will be compensated $30.00 for each study visit, for a total of up to $300.00 for those 
who complete the entire study. Subjects will not be compensated for phone calls.  
 
STATISTICAL METHODS 
 
Sample Size Determination 
The sample size for this pilot study was not based upon statistical considerations.  
Efficacy Analyses 
The efficacy analyses will be performed on an intent-to-treat (ITT) population defined as all 
randomized subjects who were dispensed study medication and for whom one post-baseline 
efficacy measurement is available. 
Efficacy analyses will be conducted separately for subjects with night eating syndrome or sleep-
related eating disorder, and across all subjects with either of these two diagnoses. The primary 
efficacy parameter will be the change in the number of nights per week of the specified 
nocturnal eating episode.  
The primary efficacy parameter of number of nights per week with nocturnal episodes will be 
analyzed using ANCOVA with baseline frequency of nocturnal episodes as a co-variate. 
Diagnostic procedures will be conducted to determine whether the statistical assumptions are 
met.  
The MOS, SDS, TFEQ, HAM-D, HbA1C, body weight and Epworth Sleepiness Scale will be 
analyzed using an ANCOVA with the baseline value as a covariate.   
Information obtained from the sleep diaries will be summarized. 
 
Safety Analyses 
 
Adverse Events 
The percent of subjects with specific treatment-emergent adverse events will be summarized by 
treatment group. 
 
Additional tabulations will be conducted to summarize those subjects who have discontinued 
treatment due to an adverse event or who experienced a severe or a serious adverse event. 
 
Clinical Laboratory Tests 
Laboratory data will be summarized by treatment group by the type of laboratory test.  


 
 
19 
 
 


 
 
20 
 
REFERENCES 
 
1. 
Winkelman, J.W. Sleep-related eating disorder and night eating syndrome: sleep 
disorders, eating disorders, or both? Sleep 2006; 29(7):949-54. 
2. 
Stunkard, A.J., Grace, W.J., & Wolff, H.G. The night-eating syndrome: A pattern of food 
intake among certain obese patients. American Journal of Medicine 1955; 19:78-86. 
3. 
Stunkard, A.J. & Allison, K.C. Two forms of disordered eating in obesity: binge eating 
and night eating. International Journal of Obesity 2003; 27:1-12. 
4. 
Stunkard, A.J.; Two eating disorders: binge eating disorder and the night eating 
syndrome. Appetite 2000; 34: 333-334. 
5. 
Winkelman, J.W.; Treatment of nocturnal eating syndrome and sleep-related eating 
disorder with topiramate. Sleep Medicine 2003; 4(3):243-6. 
6. 
 Schenck, C.H. & Mahowald, M.W.; Review of nocturnal sleep-related eating disorders. 
International Journal of Eating Disorders 1994; Vol. 15, No. 4, 343-356. 
7. 
Tucker, P.; Topiramate in the treatment of comorbid night eating syndrome and PTSD: a 
case study. Eating Disorders in press. 
8. 
Schenck C.H., Mahowald M.W. Topiramate therapy of sleep related eating disorder 
(SRED). Sleep 2006; 29(Suppl) A268.  
9. 
Winkelman, J.W. Efficacy and tolerability of open-label topiramate in the treatment of 
sleep-related eating disorder: a retrospective case series. J Clin Psychiatry 
2006;67(11):1729-34. 
10. 
TOPAMAX® (topiramate) Investigators Brochure. July 2003. 
11. 
Package Insert – TOPAMAX® (topiramate) Tablets and TOPAMAX® (topiramate 
capsules) Sprinkle Capsules. Ortho-McNeil Pharmaceutical Inc. Raritan, NJ 08869. 
REVISED June 2003. 
12. 
Lu, M.L. Shen W. W. Sleep-related eating disorder induced by risperidone. J Clin 
Psychiatry. 2004; 65(2): 273-274. 
13. 
Paquet V., Strul J. , Servais L., Pelc I, Fossion P. Sleep-related eating disorder incuded 
by olanzapine. J Clin Psychiatry. 2002; 63(7): 597. 
14. 
Schenck C.H., Hurwitz, T.D., O’Connor, K. A., Mahowald, M.W. Additional categories of 
sleep-related eating disorders and the current status of treatment. Sleep; 16(5): 457-466. 
15. 
Schenck, C.H., Connoy, D.A., Casetllanos, M. Johnson, B., Werner, R. Wills, L., Cramer 
Bornemann, M.A., Mahowald, M.W. Zolpidem-induced amnestic sleep-related eating 
disorder (SRED) in 19 patients. Sleep; 28: A259. 
  
 
 
 
 
 
 
 


21 
 
TIME AND EVENTS SCHEDULE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit 1A 
(Day 
-56) 
Visit 1 
(Day 
-14) 
Visit 2 
(Day 1) 
Visit 3 
(Day 7) 
Phone 
Contact 
(Day 
14) 
Visit 4 
(Day 
21) 
Phone 
Contact 
(Day 
28) 
Visit 5 
(Day 
35) 
Phone 
Contact 
(Day 
42) 
Visit 6 
(Day 
49) 
Phone 
Contact 
(Day 
56) 
Visit 7 
(Day 
63) 
Phone 
Contact 
(Day 
77) 
Visit 8 
(Day 
91) 
Visit 9 
(Day 
105) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review Inclusion/Exclusion 
Criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication 
Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x 
X 
X 
Medical & Psychiatric History  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neurologic Examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SCID Eating Disorders 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Urine Pregnancy Test 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
Urine Drug Screen 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood HbA1C 
 
X* 
 
 
 
 
 
 
 
 
 
 
 
X 
 
MOS 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
X 
 
Epworth Sleepiness Scale  
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
X 
 
HAM-D 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
TFEQ 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
EAT 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sheehan Disability Scale 
 
X 
 
 
 
 
 
 
 
 
 
 
 
x 
 
Dispense Sleep and Night-
Eating Diary 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Review Sleep and Night-
Eating Diary 
 
 
X 
X 
X 
X 
X 
X 
x 
X 
x 
X 
X 
X 
 
Record Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense Study Medication  
 
 
X 
X 
X 
X 
X 
X 
x 
X 
x 
X 
x 
X 
 
Collect study medication and 
perform drug accountability 
 
 
 
x 
 
x 
 
X 
 
X 
 
X 
 
x 
X 
 
*Creatinine also tested at visit 1


 
 
22 
 
 
ATTACHMENTS 
 
Attachment 1: Medical Outcome Study (MOS) Sleep Scale……………………………………22 
Attachment 2: Epworth Sleepiness Scale…………………………………………………………23 
Attachment 3: HAM-D……………………………………………………………………………..24-26 
Attachment 4: Eating Attitudes Test (EAT)…………………………………………………...27-28 
Attachment 5: Three Factor Eating Questionnaire (TFEQ)………………………………...29-31 
Attachment 6: Sheehan Disability Scale…………………………………………………………..32


 
 
23 
 
Attachment 1 
Medical Outcome Study (MOS) Sleep Scale 
 
1. 
How long did it usually take you to fall asleep during the past 4 weeks? (circle one) 
 
 
 
0-15 minutes………………... 
16-30 minutes………………. 
31-45 minutes………………. 
46-60 minutes………………. 
More than 60 minutes………. 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
 
 
2. 
On the average, how many hours did you sleep each night during the past 4 weeks? 
 
 
 
Write in # of hours per night __________ 
 
 
How often during the past 4 weeks did you…. (circle one number on each line): 
 
 
All of 
the 
Time 
Most 
of the 
Time 
A Good Bit 
of the Time 
Some of 
the 
Time 
A Little 
of the 
Time 
None of 
the 
Time 
3. 
feel that your sleep was 
not quiet (moving 
restlessly, feeling tense, 
speaking, etc., while 
sleeping)? 
1 
2 
3 
4 
5 
6 
4. 
get enough sleep to feel 
rested upon waking in the 
morning? 
1 
2 
3 
4 
5 
6 
5. 
awaken short of breath or 
with a headache? 
1 
2 
3 
4 
5 
6 
6. 
feel drowsy or sleepy 
during the day? 
1 
2 
3 
4 
5 
6 
7. 
have trouble falling 
asleep? 
1 
2 
3 
4 
5 
6 
8. 
awaken during your sleep 
time and have trouble 
falling asleep again? 
1 
2 
3 
4 
5 
6 
9. 
have trouble staying 
awake during the day? 
1 
2 
3 
4 
5 
6 
10. 
snore during your sleep? 
1 
2 
3 
4 
5 
6 
11. 
take naps (5 minutes or 
longer) during the day? 
1 
2 
3 
4 
5 
6 
12. 
get the amount of sleep 
you needed? 
1 
2 
3 
4 
5 
6 


 
 
24 
 
Attachment 2 
Epworth Sleepiness Scale 
 
How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just 
tired? This refers to your usual way of life in recent times. Even if you have not done some of 
these things recently, try to work out how they would have affected you. 
 
 
Use the following scale to choose the most appropriate number for each situation: 
 
 
 
 
 
0 = 
Would never doze 
 
 
 
 
1 = 
Slight chance of dozing 
 
 
 
 
2 =  
Moderate chance of dozing 
 
 
 
 
3 = 
High chance of dozing 
 
 
 
SITUATION 
 
 
 
 
 
 
CHANCE OF DOZING 
 
Sitting and reading 
 
 
 
 
 
 
 
 
 
 
Watching TV 
 
 
 
 
 
 
 
 
 
 
 
Sitting, inactive in a public place (e.g. a theatre or a meeting) 
 
 
 
 
 
As a passenger in a car for an hour without a break 
 
 
 
 
 
 
Lying down to rest in the afternoon when circumstances permit  
 
 
 
 
Sitting and talking to someone  
 
 
 
 
 
 
 
 
Sitting quietly after lunch without alcohol 
 
 
 
 
 
 
 
In a car, while stopped for a few minutes in traffic 
 
 
 
 
 
 
 
 
 
 
 
 
Total Score: 
 
 
 
 
 
 
EPWORTH SLEEPINESS SCALE SCORE 
 
A score of <8 
indicates normal sleep function 
A score of 8-10 
indicates mild sleepiness 
A score of 11-15 
indicates moderate sleepiness 
A score of 16-20 
indicates severe sleepiness 
A score of 21-24 
indicates excessive sleepiness 


 
 
25 
 
Attachment 3: Hamilton Rating Scale for Depression (HAM-D) 
 
1. Depressed mood (Sadness, hopeless, helpless, worthless) 
0 = Absent 
1 = Gloomy attitude, pessimism, hopelessness 
2 = Occasional weeping 
3 = Frequent weeping 
4 = Patient reports highlight these feelings states in his/her spontaneous verbal and  
      non-verbal communication. 
  
2. Feelings of guilt 
0 = Absent 
1 = Self-reproach, feels he/she has let people down 
2 = Ideas of guilt or rumination over past errors or sinful deeds 
3 = Present illness is punishment 
4 = Hears accusatory or denunciatory voices and/or experiences threatening visual hallucinations. 
      Delusions of guilt. 
  
3. Suicide 
0 = Absent 
1 = Feels life is not worth living 
2 = Wishes he/she were dead, or any thoughts of possible death to self 
3 = Suicide, ideas or half-hearted attempt 
4 = Attempts at suicide (any serious attempt rates 4) 
  
4. Insomnia, early  
0 = No difficulty falling asleep 
1 = Complaints of occasional difficulty in falling asleep i.e. more than half-hour 
2 = Complaints of nightly difficulty falling asleep 
  
5. Insomnia, middle  
0 = No difficulty 
1 = Patient complains of being restless and disturbed during the night 
2 = Walking during the night – any getting out of bed rates 2 (except voiding bladder) 
  
6. Insomnia, late  
0 = No difficulty 
1 = Waking in the early hours of the morning but goes back to sleep 
2 = Unable to fall asleep again if he/she gets out of bed  
 
7. Work and activities 
0 = No difficulty 
1 = Thoughts and feelings of incapacity related to activities: work or hobbies 
2 = Loss of interest in activity – hobbies or work – either directly reported by patient or 
      indirectly seen in listlessness, in decisions and vacillation (feels he/she has to push 
      self to work or activities) 
3 = Decrease in actual time spent in activities or decrease in productivity. In hospital, 
      rate 3 if patient does not spend at leas three hours a day in activities 
4 = Stopped working because of present illness. In hospital rate 4 if patient engages 
      in no activities except supervised ward chores 
  
8. Retardation : Psychomotor (Slowness of thought and speech; impaired ability to concentrate; 
decreased motor activity) 
0 = Normal speech and thought 
1 = Slight retardation at interview 
2 = Obvious retardation at interview 


 
 
26 
 
3 = Interview difficult 
4 = Interview impossible 
 
9. Agitation  
0 = None 
1 = Fidgetiness 
2 = Playing with hands, hair, obvious restlessness 
3 = Moving about; can’t sit still 
4 = Hand wringing, nail biting, hair pulling, biting of lips, patient is on the run 
 
10. Anxiety, psychic  
Demonstrated by: subjective tension and irritability, loss of concentration, worrying about minor matters, 
apprehension, fears expressed without questioning, feelings of panic, feeling jumpy  
0 = Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
4 = Incapacitating 
11. Anxiety, somatic  
Physiological concomitants of anxiety such as: 
• gastrointestinal,:dry mouth, wind, indigestion, diarrhea, cramps, belching  
• cardiovascular: palpations, headaches  
• respiratory: hyperventilation, sighing  
• urinary frequency  
• sweating  
• giddiness, blurred vision  
• tinnitus  
0 = Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
4 = Incapacitating 
 
12. Somatic symptoms: gastro-intestinal 
0= None 
1= Loss of appetite but eating without encouragement from others. Food intake about normal.  
2= Difficulty eating without urging from others.  Marked reduction of appetite and food intake.  
 
13. Somatic symptoms: general  
0 = None 
1 = Heaviness in limbs, back or head; backaches, headaches, muscle aches, loss of energy, 
      fatigability 
2 = Any clear-cut symptom rates 2 
 
14. Genital Symptoms 
Symptoms such as: loss of libido, menstrual disturbances 
0 = Absent 
1 = Mild 
2 = Severe 
  
15. Hypochondriasis  
0 = Not present 
1 = Self-absorption (bodily) 
2 = Preoccupation with health 
3 = Strong conviction of some bodily illness 
4 = Hypochondrial delusions 


 
 
27 
 
 
16. Loss of Weight  
Rate either ‘A’ or ‘B’: 
 
A When rating by history: 
0 = No weight loss 
1 = Probable weight loss associated with present illness 
2 = Definite (according to patient) weight loss 
 
B Actual weight changes (weekly): 
0 = Less than 1 lb (0.5 kg) weigh loss in one week 
1 = 1-2 lb (0.5 kg-1.0 kg) weight loss in week 
2 = Greater than 2 lb (1 kg) weight loss in week 
3 = Not assessed 
  
17. Insight  
0 = Acknowledges being depressed and ill 
1 = Acknowledges illness but attributes cause to bad food, overwork, virus, need for rest, etc. 
2 = Denies being ill at all 
 
 
 
TOTAL SCORE: ___ 
 


 
 
28 
 
Attachment 4: Eating Attitudes Test (EAT) 
 
 
*Please do not consider episodes of eating while you are asleep when 
answering this questionnaire* 
 
Please check a response for each of the following statements: 
(continued on next page) 
 
 
 
 
 
 
 
 
 
I . . . 
 
Always 
 
Usually 
 
Often 
 
Sometimes 
 
Rarely 
 
Never 
1. Am terrified about being overweight. 
 
□ 
□ 
□ 
□ 
□ 
□ 
2. Avoid eating when I am hungry. 
 
□ 
□ 
□ 
□ 
□ 
□ 
3. Find myself preoccupied with food. 
 
□ 
□ 
□ 
□ 
□ 
□ 
4. Have gone on eating binges where I 
feel that I may not be able to stop. 
 
□ 
□ 
□ 
□ 
□ 
□ 
5. Cut my food into small pieces. 
 
□ 
□ 
□ 
□ 
□ 
□ 
6. Aware of the calorie content of foods 
that I eat. 
 
□ 
□ 
□ 
□ 
□ 
□ 
7. Particularly avoid food with a high 
carbohydrate content (i.e. bread, rice, 
potatoes,etc.) 
 
□ 
□ 
□ 
□ 
□ 
□ 
8. Feel that others would prefer if I ate 
more. 
 
□ 
□ 
□ 
□ 
□ 
□ 
9. Vomit after I have eaten. 
 
□ 
□ 
□ 
□ 
□ 
□ 
10. Feel extremely guilty after eating. 
 
□ 
□ 
□ 
□ 
□ 
□ 
11. Am preoccupied with a desire to be 
thinner. 
 
□ 
□ 
□ 
□ 
□ 
□ 
12. Think about burning up calories when 
I exercise. 
 
□ 
□ 
□ 
□ 
□ 
□ 
13. Other people think that I am too thin. 
 
□ 
□ 
□ 
□ 
□ 
□ 
14. Am preoccupied with the thought of 
having fat on my body. 
 
□ 
□ 
□ 
□ 
□ 
□ 


 
 
29 
 
 
 
 
 
 
Attachment 4: Eating Attitudes Test (EAT) 
continued 
 
*Please do not consider episodes of eating while you are asleep when 
answering this questionnaire* 
 
Please check a response for each of the following statements: 
 
 
Total Score______
I . . . 
 
Always 
 
Usually 
 
Often 
 
Sometimes 
 
Rarely 
 
Never 
15. Take longer than others to eat my 
meals. 
 
□ 
□ 
□ 
□ 
□ 
□ 
16. Avoid foods with sugar in them. 
 
□ 
□ 
□ 
□ 
□ 
□ 
17. Eat diet foods. 
 
□ 
□ 
□ 
□ 
□ 
□ 
18. Feel that food controls my life. 
 
□ 
□ 
□ 
□ 
□ 
□ 
19. Display self-control around food. 
 
□ 
□ 
□ 
□ 
□ 
□ 
20. Feel that others pressure me to eat. 
 
□ 
□ 
□ 
□ 
□ 
□ 
21. Give too much time and thought to 
food. 
 
□ 
□ 
□ 
□ 
□ 
□ 
22. Feel uncomfortable after eating 
sweets. 
 
□ 
□ 
□ 
□ 
□ 
□ 
23. Engage in dieting behavior. 
 
□ 
□ 
□ 
□ 
□ 
□ 
24. Like my stomach to be empty. 
 
□ 
□ 
□ 
□ 
□ 
□ 
25. Have the impulse to vomit after meals. 
 
□ 
□ 
□ 
□ 
□ 
□ 
26. Enjoy trying new rich foods. 
 
□ 
□ 
□ 
□ 
□ 
□ 


 
 
30 
 
Attachment 5: Three Factor Eating Questionnaire (TFEQ) 
 
*Please do not consider episodes of eating while you are asleep when answering this questionnaire* 
 
Part I: Read each of the following 36 statements carefully. If you agree with the statement or feel that it 
is true as applied to you; answer true by circling the appropriate letter (T).  If you disagree with the 
statement, or feel that it is false as applied to you, answer false by circling the appropriate letter (F).   
 
1. When I smell a sizzling steak or see a juicy piece of meat, I find it very 
difficult to keep from eating, even if I have just finished a meal.  
T 
F 
2. I usually eat too much at social occasions, like parties and picnics. 
T 
F 
3. I am usually so hungry that I eat more than three times a day. 
T 
F 
4. When I have eaten my quota of calories, I am usually good about not eating 
anymore. 
T 
F 
5. Dieting is so hard for me because I just get too hungry. 
T 
F 
6. I deliberately take small helpings as a means of controlling my weight. 
T 
F 
7. Sometimes things just taste so good that I keep on eating even when I am no 
longer hungry. 
T 
F 
8. Since I am often hungry, I sometimes wish that while I am eating, an expert 
would tell me that I have had enough or that I can have something more to 
eat. 
T 
F 
9. When I feel anxious, I find myself eating.  
T 
F 
10. Life is too short to worry about dieting.  
T 
F 
11. Since my weight goes up and down, I have gone on reducing diets more than 
once.  
T 
F 
12. I often feel so hungry that I just have to eat something.  
T 
F 
13. When I am with someone who is overeating, I usually overeat too.  
T 
F 
14. I have a pretty good idea of the number of calories in common foods.  
T 
F 
15. Sometimes when I start eating, I just can’t seem to stop.  
T 
F 
16. It is not difficult for me to leave something on my plate.  
T 
F 
17. At certain times of the day, I get hungry because I have gotten used to eating 
then.  
T 
F 
18. While on a diet, if I eat a food that is not allowed, I consciously eat less for a 
period of time to make up for it.  
T 
F 
19. Being with someone who is eating often makes me hungry enough to eat 
also.  
T 
F 
20. When I feel blue, I often overeat.  
T 
F 
21. I enjoy eating too much to spoil  it by counting calories or watching my 
weight.  
T 
F 
22. When I see a real delicacy, I often get so hungry that I have to eat right away.   T 
F 
23. I often stop eating when I am not really full as a conscious means of limiting 
the amount that I eat. 
T 
F 
24. I get so hungry that my stomach often seems like a bottomless pit.  
T 
F 
25. My weight has hardly changed at all in the last ten years.  
T 
F 
26. I am always hungry so it is hard for me to stop eating before I finish the food 
on my plate.  
T 
F 
27. When I feel lonely, I console myself by eating.  
T 
F 
28. I consciously hold back at meals in order not to gain weight.  
T 
F 
29. I sometimes get very hungry late in the evening or at night.  
T 
F 
30. I eat anything I want, any time I want.  
T 
F 
31. Without even thinking about it, I take a long time to eat.  
T 
F 
32. I count calories as a conscious means of controlling my weight.  
T 
F 
33. I do not eat some foods because they make me fat.  
T 
F 
34. I am always hungry enough to eat at any time.  
T 
F 
35. I pay a great deal of attention to changes in my figure.  
T 
F 
36. While on a diet, if I eat a food that is not allowed, I often then splurge and eat 
T 
F 


 
 
31 
 
other high calorie foods.  
 
 
Part II.  Each question I this section is followed by a number of answer options.  After reading each 
question carefully, choose the one option which most applies to you and circle the appropriate number.   
 
37. How often are you dieting in an conscious 
effort to control your weight? 
1 
Rarely 
2 
Sometime
s 
3 
Usually 
4 
Always 
38. Would a weight fluctuation of 5 lbs. affect 
the way you live your life? 
1 
Not at 
all 
2 
Slightly 
3 
Moderatel
y 
4 
Very 
Much 
39. How often do you feel hungry? 
1 
Only at 
meal 
times 
2 
Sometime
s between 
meals 
3 
Often 
between 
meals 
1 
Almost 
always 
40. Do your feelings of guilt about overeating 
help you to control your food intake? 
1 
Never 
2 
Rarely 
3 
Often 
4 
Always 
41. How difficult would it be for you to stop 
eating halfway through dinner and not eat 
for the next four hours? 
1 
Easy 
2 
Slightly 
difficult 
3 
Moderatel
y difficult 
4 
Very 
Difficult 
42. How conscious are you of what you are 
eating? 
1 
Not at all 
2 
Slightly 
3 
Moderately 
4 
Very 
Much 
43. How frequently do you avoid “stocking up” 
on tempting foods? 
1 
Almost 
never 
2 
Seldom 
3 
Usually 
4 
Almost 
Always 
44. How likely are you to shop for low calorie 
foods? 
1 
Unlikely 
2 
Slightly 
likely 
3 
Moderatel
y likely 
4 
Very 
likely 
45. Do you eat sensibly in front of other and 
splurge alone? 
1 
Never 
2 
Rarely 
3 
Often 
4 
Always 
46. How likely are you to consciously eat 
slowly in order to cut down on how much 
you eat? 
1 
Unlikely 
2 
Slightly 
likely 
3 
Moderately 
likely 
4 
Very 
likely 
47. How frequently do you skip dessert because 
you are no longer hungry? 
1 
Almost 
never 
2 
Seldom 
3 
At least 
once a 
week 
4 
Almost 
every day 
48. How likely are you to consciously eat less 
than you want? 
1 
Unlikely 
2 
Slightly 
likely 
3 
Moderatel
y likely 
4 
Very 
likely 
49. Do you go on eating binges even though 
you are not hungry? 
1 
Never 
2 
Rarely 
3 
Sometimes 
4 
At least 
once a 
week 
50. To what extent does this statement describe 
your eating behavior? 
“I start dieting in the morning, but because of 
any number of things that happen during the 
day, by evening I have given up and eat what I 
want, promising myself to start dieting again 
tomorrow.” 
 
1 
Not like 
me 
2 
Little like 
me 
3 
Pretty 
good 
descriptio
n of me 
4 
Describe
s me 
perfectly 
 
 


 
 
32 
 
 
Part III:  
 
51. On a scale of 1 to 6, where 1 means no restraint in eating (eat whatever you want, whenever 
you want it) and 6 means total restraint (constantly limiting food intake and never “giving in”), 
what number would you give yourself? 
 
1. eat whatever you want, whenever you want it 
2. usually eat whatever you want, whenever you want it 
3. often eat whatever you want, whenever you want it 
4. often limit food intake, but often “give in” 
5. usually limit food intake, rarely “give in” 
6.   constantly limiting food intake, never “giving in”


 
 
33 
 
 
 Attachment 6:  
Sheehan Disability Scale (SDS)  
 
Instructions: Please mark ONE box for each scale based on your symptoms over the past week. 
 
 
WORK / SCHOOL 
 
The symptoms have disrupted your work / school work:  
 
 
 
 
 
SOCIAL LIFE 
 
The symptoms have disrupted your social life: 
 
 
 
 
 
FAMILY LIFE / HOME RESPONSIBILITIES 
 
The symptoms have disrupted your family life/home responsibilities: 
 
 
 
0
1
2
3
4
5
6
7
8
9
10
Not at all
Mildly
Moderately
Markedly
Extremely
0
1
2
3
4
5
6
7
8
9
10
Not at all
Mildly
Moderately
Markedly
Extremely
0
1
2
3
4
5
6
7
8
9
10
Not at all
Mildly
Moderately
Markedly
Extremely


 
 
34 
 
 
 
 
Please answer the following questions about how much your symptoms of 
Sleep-Related Eating Disorder affect you emotionally. 
 
 
 
1. How worried or distressed are you by your symptoms of Sleep-Related Eating Disorder?  
(circle one number) 
 
Not Worried 
 
 
 
 
 
                        
 
                  Very Worried 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
 10 
 
 
 
2. How ashamed are you of your symptoms of Sleep-Related Eating Disorder?  
(circle one number) 
 
Not Ashamed 
 
 
 
 
 
                        
 
               Very Ashamed 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
 10