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

Obesity Clinical Trial

Official title:

Pharmacologic Weight Loss as Adjunct Therapy for Ulcerative Colitis in Obese Patients: A Phase 2A, Randomized, Placebo-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04721873
• Other study ID #: 190419
• Secondary ID: 623346
• Status: Recruiting
• Phase: Phase 2
• Start date: December 18, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: May 2023
• Source: University of California, San Diego
• Contact: Siddharth Singh, MD
• Phone: 8582462352
• Email: sis040[@]ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 (TNFa 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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Obesity
• Ulcer
• Weight Loss

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	University of California San Diego	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight loss - 5%	Proportion of patients with =5% weight loss over baseline	22 weeks
Secondary	Weight loss - 10%	Proportion of patients with =10% weight loss over baseline	22 weeks
Secondary	Absolute weight loss	Absolute weight loss from baseline	22 weeks
Secondary	Discontinuation	Discontinuation of therapy due to treatment-related adverse events	22 weeks
Secondary	Corticosteroid-free clinical remission	PRO2 remission, with no prednisone use within 1 week of assessment	22 weeks
Secondary	Biochemical remission	Fecal calprotectin (FC) =50µg/g	22 weeks