Pharmacologic Weight Loss as Adjunct Therapy for Ulcerative Colitis in Obese Patients

University of California San Diego

Status and phase

Enrolling

Phase 2

Conditions

Colitis, Ulcerative

Obesity

Treatments

Drug: Phentermine-Topiramate

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT04721873

623346 (Other Grant/Funding Number)

190419

Details and patient eligibility

About

Approximately 20-40% of patients with ulcerative colitis (UC) are obese. The investigators have demonstrated that obesity adversely impacts disease course in patients with UC, leading to higher risk of persistently active disease, surgery, hospitalization, and treatment failure, particularly in biologic-treated patients. Intentional weight loss is effective in improving disease outcomes in patients with inflammatory arthritis, but there is limited data on its impact in UC. While dietary interventions for weight loss have limited efficacy and endoscopic bariatric interventions may be too invasive in patients with UC with active gastrointestinal symptoms, pharmacological weight loss with a highly effective oral agent may be a novel strategy to induce weight loss and augment the efficacy of biologic therapy in UC.

Hence, the investigators are conducting a pilot, phase 2A, 22-week, randomized, placebo-controlled clinical trial of phentermine-topiramate in obese patients with active UC starting on a new biologic agent (infliximab, adalimumab, golimumab, vedolizumab).

The overall objective is to (1) evaluate the efficacy, safety and tolerability of phentermine-topiramate, and (2) to assess the impact of pharmacological weight loss on clinical outcomes, inflammatory burden and biologic trough concentration in patients with UC. The central hypothesis is that phentermine-topiramate will be safe, effective, and well tolerated in patients with UC, and weight loss would achieve higher rates of clinical and biochemical remission, and higher biologic trough concentration.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

adults aged 18-80y
BMI ≥30kg/m^2
established diagnosis of UC based on clinical and endoscopy evidence corroborated by histopathology report
active UC (Mayo Clinic score [MCS], 6-12; or active disease based on rectal bleeding score [RBS]=2 or 3 and stool frequency score=2 or 3) or dependent on corticosteroids (unable to taper below 10mg prednisone equivalent, or flaring within 2 months of stopping prednisone)
starting a new biologic agent (TNFα antagonists, vedolizumab, ustekinumab) or flaring despite stable maintenance dose of biologic agent
stable weight (<5kg weight change) for preceding 4 weeks prior to screening and randomization
able to speak or understand English and provide written informed consent.

Exclusion criteria

pregnant or lactating women
prisoners
current or history of toxic megacolon, abdominal abscess, symptomatic intestinal or colonic stricture, history of colectomy or diverting stoma, short bowel syndrome, active tuberculosis or other bacterial infections, cancer
any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise patient safety
clinically meaningful laboratory abnormalities, including significant anemia (Hb<8g/dl), leukopenia (<3x10^9/L), thrombocytopenia (<100K) or thrombocytosis (>600K), ALT/AST >3x upper limit of normal, creatinine >2x upper limit of normal
blood pressure >140/95mmHg (ok to include if BP controlled on anti-hypertensives), fasting blood glucose >240mg/dl or HbA1c >9%, fasting triglycerides >400mg/dl at randomization, type 1 diabetes, coronary artery disease, stroke, or other symptomatic peripheral arterial disease
history of nephrolithiasis (H/O kidney stone >1 time, and kidney stone within 1y prior to start of study), hyperthyroidism, seizure disorder
recurrent major depression, presence or history of suicidal behavior or ideation with intent to act, current substantial depressive symptoms (patient health questionnaire-9, ≥10), use of antidepressant medication that has not been stable for the prior 3 months (bupropion-treated patients will be excluded)
history of (or treatment for) glaucoma or increased intraocular pressure
prior bariatric surgery; >5 kg weight fluctuation in preceding 4 weeks, use of very-low-calorie diet, or participation in a formal weight loss program in the 3 months prior to the study
smoking cessation within previous 3 months or plans to quit during the study period
history of eating disorder or drug/alcohol abuse within the preceding 1 year concomitant use of other sympathomimetic medications, for example for ADHD
known allergy to study medication