Pharmacological and Behavioral Treatment After Bariatric Surgery: Medication Change for Non-Responders (Stage 2b)

• Lisdexamfetamine Dimesylate (Medication) (Drug), also known as Vyvanse: Medication will be taken daily in pill form.
• Placebo (Other): Placebo will be inactive and taken daily in pill form.

Primary outcomes

• Loss-of-Control Eating Frequency [At the end of 12-week treatment]: Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Loss-of-control eating frequency will be based on the past 28 days and defined as loss-of-control eating episodes per month.
• Loss-of-Control Eating Frequency [6-month follow-up from the end of treatment]: Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Loss-of-control eating frequency will be based on the past 28 days and defined as loss-of-control eating episodes per month.
• Loss-of-Control Eating Frequency [12-month follow-up from the end of treatment]: Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Loss-of-control eating frequency will be based on the past 28 days and defined as loss-of-control eating episodes per month.
• Percent Weight Change [From baseline at study enrollment to after the 12-week treatment]: Percent weight loss is calculated based on change from pre-treatment to post-treatment at 3 months. Negative values indicate weight loss.
• Percent Weight Change [From post-treatment to the 6-month follow-up]: Percent weight loss is calculated based on change from post-treatment to the 6-month follow-up. Negative values indicate weight loss.
• Percent Weight Change [From post-treatment to the 12-month follow-up]: Percent weight loss is calculated based on change from post-treatment to the 12-month follow-up. Negative values indicate weight loss.

Sex: All, ages: 18 Years to 64 Years

Inclusion Criteria:

* Be in the age range ≥18 years of age and <65 years of age.
* Have had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy
* Approximately ten months post-surgery
* Experienced regular loss of control eating about six months after bariatric surgery, and were considered treatment non-responders to a four-month treatment trial of medication and/or BWL
* Be an otherwise healthy subject without uncontrolled medical problems, as determined by the study physician and medical co-investigators (physical examination, laboratory studies).
* Read, comprehend, and write English at a sufficient level to complete study-related materials.
* Provide a signed and dated written informed consent prior to study participation.
* Be available for participation in the study for up to 15 months (3-month treatment plus 12-month follow up).

Exclusion Criteria:

* Has a predisposition to seizures (e.g., subject with a history or evidence of seizure disorder, febrile seizures during childhood, brain tumor, cerebrovascular disease, or significant head trauma; has a family history of idiopathic seizure disorder or is currently being treated with medications or treatment regimens that lower seizure threshold).
* Has a history of anorexia nervosa or history of bulimia nervosa.
* Is currently using other medications for weight loss.
* Has a co-existing psychiatric condition that requires hospitalization or more intensive treatment (such as bipolar mood disorders, psychotic illnesses, or severe depression)
* Has untreated hypertension with a seated systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg, or heart rate > 100 beats/minute.
* Has a history of congenital heart disease, cardiovascular disease, cardiac arrhythmias requiring medication, or a history of cerebrovascular pathology including stroke.
* Has current uncontrolled hypertension.
* Has current uncontrolled Type I or Type II diabetes mellitus.
* Has untreated hypothyroidism with a TSH > 1.5 times the upper limit of normal for the test laboratory with repeat value that also exceeds this limit.
* Has gallbladder disease.
* Has a history of severe renal, hepatic, neurological, chronic pulmonary disease, or any other unstable medical disorder.
* Is currently in active treatment for eating or weight loss.
* Is currently participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug or device.
* Is breast-feeding or is pregnant or is not using a reliable form of birth control.
* Reports active suicidal or homicidal ideation.
* Previous history of problems with LDX or other stimulants.
* Has a history of allergy or sensitivity to LDX or other stimulant medications.
* Current medication contraindicated with study medication.
* Any current psychostimulant use or any medication for ADHD.
* History or current alcohol or substance use disorder (smoking will not be exclusionary)
* Is currently taking MAOI medication, SSRI medication, or strong inhibitors of CYP2D6

Participant flow

Outcome results

• Loss-of-Control Eating Frequency (Primary), Mean, episodes per the past 28 days: Lisdexamfetamine Dimesylate 6.11 +/- 6.72; Placebo 11.25 +/- 10.31
• Loss-of-Control Eating Frequency (Primary), Mean, episodes per the past 28 days: Lisdexamfetamine Dimesylate 10.50 +/- 4.80; Placebo 10.00 +/- 6.00
• Loss-of-Control Eating Frequency (Primary), Mean, episodes per the past 28 days: Lisdexamfetamine Dimesylate 7.67 +/- 3.79; Placebo 1.67 +/- 2.08
• Percent Weight Change (Primary), Mean, percent change: Lisdexamfetamine Dimesylate -3.80 +/- 3.72; Placebo 4.37 +/- 1.97
• Percent Weight Change (Primary), Mean, percent change: Lisdexamfetamine Dimesylate -1.13 +/- 7.63; Placebo 6.36 +/- 4.00
• Percent Weight Change (Primary), Mean, percent change: Lisdexamfetamine Dimesylate 3.91 +/- 7.35; Placebo 9.07 +/- 2.75

Adverse events

Time frame: From enrollment to the end of the 12 week treatment

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2023-06-21)

• Carlos Grilo, PhD, Principal investigator, Yale University

NIH grants: R01DK126637