LOSS- Louisiana Obese Subjects Study

LOSS is a pragmatic clinical trial designed to evaluate intensive medical treatment for
patients with severe obesity who would otherwise qualify as candidates for obesity surgery
and who are covered by the Louisiana Office of Group Benefits (OGB) Health Insurance. LOSS
will track the efficacy, safety and costs to compare two patient management approaches -
intensive medical treatment, or a usual medical care treatment model. Recruitment will be
done by mailers to insured patients to identify eligible candidates. We will randomly assign
eligible volunteers to intensive medical treatment (n=240) or usual care (n=240). Patients
will be evaluated annually and medical treatments are given in eight clinics around
Louisiana. The eight sites are in Alexandria, Baton Rouge, Lafayette, Lake Charles, Monroe,
Hammond, New Orleans and Shreveport.

Hypothesis:

We hypothesize that we can achieve weight loss after two and five years that exceeds 20%
from baseline with intensive medical management of persons with class III obesity and that
this weight loss is greater than that achieved with usual medical care including access to a
weight management web site.

Our secondary hypotheses are: 1) that the weight loss at year 2 and 5 in the intensive
medical group is associated with improvements in blood pressure, fasting glucose, lipids,
health-related quality of life and psychosocial measures and is greater improvement than
that achieved with usual medical care and access to a website; and 2) that total medical
costs in the intensive medical management group will compare favorably to total medical
costs in the usual care group (i.e., total reimbursement from insurance costs will be less,
even when the expense of the treatment is considered).

Overall Aim:

The overarching aim of this study is to observe the effect of an intensive medical
management program versus usual care for class III obesity on weight loss, total medical
costs and, on measures of health risks associated with weight loss (blood pressure, blood
glucose, blood lipids, and health-related quality of life).

Specific Aims:

Primary: The primary specific aim of the LOSS study is to test the hypothesis that the
weight loss efficacy at years 2 and 5 for an intensive medical treatment program for Class
III obesity produces greater weight loss, as compared to a condition of usual care.

Secondary: The secondary aims of the study are:

- To evaluate the percent change in body weight, absolute change in body weight
(kilograms) and percent excess weight lost from baseline at months 3, 6, 12, 24, 36, 48
and 60 for medically treated patient groups, and at years 1, 2, 3, 4 and 5 for both
groups.

- To evaluate the number and proportion of subjects who maintain 100% and 80% of 12
months weight lost at months 24, 36, 48 and 60 for medically treated patients and at
years 2, 3, 4 and 5 for both groups.

- To evaluate the changes from baseline in blood pressure, pulse rate, and efficacy
laboratory parameters at visits on months 3, 6, 12, 24, 36, 48 and 60 for the medically
treated patient group, and at years 1, 2, 3, 4 and 5 for both groups.

- To assess the safety and tolerability of the intervention regimens at months 3, 6, 12,
24, 36, 48 and 60 for the medically treated patient group.

- To assess the total medical costs of the participants treated with intensive medical
treatment and for the patients receiving usual care at years 1, 2, 3, 4 and 5.

- To assess additional psychosocial and economic measures (health-related quality of
life, pain, depression, and stress) for the intervention group at months 4, 8, 12, 24,
36, 48 and 60 months for both groups at years 1, 2, 3, 4, and 5.

- To compare subgroups of patients with class III obesity to determine if differences in
outcome exist for gender, race, education level, decades of age and presence of
co-morbid conditions.

The Pennington Biomedical Research Center is the lead institution for the project.
Pennington Management of Clinical Trials (PMCT) will serve as the Coordinating Center to
manage enrollment and data acquisition and will report all data of health and cost results
to a Data Safety Monitoring Board on a regular basis. Major data reports and scientific
publications occur at years 2 and 5.

Inclusion Criteria:

- Participant in the Exclusive Provider Organization (EPO), Managed Care Organization
(MCO) and Preferred Provider Organization (PPO) programs of the Louisiana State
Employees Group Benefits Health Insurance

- Agree to travel for treatment to the assigned study site

- Agree to randomized treatment assignment

- Male and females age 20-60 years

- Body Mass Index >40kg/m2 but < 60 kg/m2

- Females must be non-pregnant and using an approved contraception method

- Complete Blood Count (CBC): normal hematocrit, white count and platelet count, unless
waived by Principal Investigator (PI)

- Uric Acid <9.0 mg/dl

- Normal Creatinine

- Normal Thyroid Stimulating Hormone (TSH)

- Negative urine pregnancy test for women of childbearing potential

- Able to give written informed consent

- Able to comply with study procedures

Exclusion Criteria:

Factors that may limit adherence to interventions or affect conduct of the trial:

- Unable or unwilling to give informed consent or communicate with local study staff

- Hospitalization for psychiatric illness or substance use/abuse within the past year

- Self-report of alcohol or substance abuse within the past twelve months

- Current major depressive episode or history of suicidal behaviors

- Endorsement of significant recent suicidal ideation (as determined by PI)

- Travel plans that do not permit participation

- History of prior bariatric surgery, small bowel resection, or extensive bowel
resection

- Current use of chronic systemic corticosteroids, appetite suppressants, antipsychotic
medication, herbal medications for weight loss or any medication not approved by the
PI.

- Another member of the household is a participant or staff member in the study

- History of eating disorder such as anorexia nervosa, bulimia, or binge eating

- Diagnosis of schizophrenia, other psychotic disorders, bipolar disorder, or
personality disorder (as determined by the PI)

- Currently pregnant or nursing or plans to become pregnant in the next five years

- Except for non-melanoma skin cancer, cancer requiring treatment in the past five
years, unless the prognosis is excellent

- Self report of Human Immunodeficiency Virus (HIV) positive, hepatitis C or active
tuberculosis

- Cardiovascular disease event within the past year

- Severe congestive heart failure (New York Heart Association [NYHA] Functional Class
III, IV)

- Second degree or greater heart block

- Blood Pressure >160 systolic or >100 diastolic on two consecutive visits, unless
treated and re-screened

- Based upon responses to psychological screening or an interview, patients may be
excluded by the study psychologist.

- Other medical, psychiatric, or behavioral limitations that in the judgment of the
investigator may interfere with study participation or the ability to follow the
intervention protocol.

- Pregnancy is to be avoided during the study. Women who have not had a hysterectomy or
oophorectomy must have a negative urine pregnancy test result at screening. Women of
childbearing potential will be allowed to participate if they have undergone tubal
ligation, or use one of the following types of contraception: properly used condom or
diaphragm, oral contraceptives, hormonal implant, or intrauterine device (IUD).
Sexual abstinence may constitute an acceptable birth control method for this study
with investigator approval. Women with male partners who have had a successful
vasectomy (more than one year of unprotected sexual intercourse without pregnancy)
are not required to use additional birth control methods as long as the relationship
remains exclusive, and the woman agrees to use an approved contraception method with
any other male partner. Questions regarding individual patient contraceptive
practices should be directed to the Principal Investigator.