RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2020-12-18

Study Completion:2024-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04721873

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Study Contact

Siddharth Singh, MD

CONTACT

8582462352

sis040@ucsd.edu

Study Locations (Sites)

University of California San Diego

La Jolla, California, 92037

United States

Collaborators and Investigators

Sponsor: University of California, San Diego

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-18

Study Completion Date2024-06-30

Study Record Updates

Study Start Date2020-12-18

Study Completion Date2024-06-30

Terms related to this study

Additional Relevant MeSH Terms

Colitis, Ulcerative
Obesity