Recruiting

Phase 2

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

Sponsor:

UCLA

Code:

NCT04721873

Conditions

Colitis, Ulcerative

Obesity

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Phentermine-Topiramate

Placebo

Study Details

Brief summary:

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.

Conditions

Colitis, Ulcerative

Obesity

Study ID

NCT04721873

Start date

Dec 18, 2020

Status verified date

May, 2023

Completion date

Jun 30, 2024

Anticipated

Primary completion date

Jun 30, 2024

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Intervention

placebo comparator: Placebo

Interventions

Phentermine-Topiramate

Patients will be randomized to either once-daily, oral phentermine-topiramate 15-92mg or placebo, in a 1:1 fashion, for 22 weeks, with clinic visits with an obesity medicine specialist, for intensive counseling for diet and lifestyle intervention. All patients will be dose-titrated within the first 4 weeks, starting at phentermine-topiramate 3.75-23mg, or placebo. Dose titration will be performed as follows 3.75-23mg x 1 week --> 7.5-46mg x 1 week --> 11.25-69mg x 1 week --> 15-92mg. Patients who experience side effects would undergo slower titration, and dose would be down-titrated and capped at highest tolerated dose.

Placebo

Matching placebo, titrated as active intervention

Primary outcome measure

Weight loss - 5% [ Time Frame: 22 weeks ]

Central Contacts and Locations

Central contacts

Siddharth Singh, MD

8582462352 sis040@ucsd.edu

Locations

University of California San Diego

Recruiting

La Jolla, California, United States, 92037

Contacts

Siddharth Singh

858-246-2352 sis040@ucsd.edu

sis040@ucsd.edu

Principal Investigator:

Siddharth Singh, MD

More Information

Sponsor

University of California, San Diego

Last update posted

May 16, 2023

Last verified

May, 2023

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, San Diego on 2023-05-16.