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

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ClinicalTrials.gov Identifier: NCT04721873
Recruitment Status : Recruiting
First Posted : January 25, 2021
Last Update Posted : January 27, 2021
Sponsor:
Information provided by (Responsible Party):
Siddharth Singh, University of California, San Diego

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.


Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Obesity Drug: Phentermine-Topiramate Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacologic Weight Loss as Adjunct Therapy for Ulcerative Colitis in Obese Patients: A Phase 2A, Randomized, Placebo-Controlled Trial
Actual Study Start Date : December 18, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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 Comparator: Placebo Drug: Placebo
Matching placebo, titrated as active intervention




Primary Outcome Measures :
  1. Weight loss - 5% [ Time Frame: 22 weeks ]
    Proportion of patients with ≥5% weight loss over baseline


Secondary Outcome Measures :
  1. Weight loss - 10% [ Time Frame: 22 weeks ]
    Proportion of patients with ≥10% weight loss over baseline

  2. Absolute weight loss [ Time Frame: 22 weeks ]
    Absolute weight loss from baseline

  3. Discontinuation [ Time Frame: 22 weeks ]
    Discontinuation of therapy due to treatment-related adverse events

  4. Corticosteroid-free clinical remission [ Time Frame: 22 weeks ]
    PRO2 remission, with no prednisone use within 1 week of assessment

  5. Biochemical remission [ Time Frame: 22 weeks ]
    Fecal calprotectin (FC) ≤50μg/g



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04721873


Contacts
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Contact: Siddharth Singh, MD 8582462352 sis040@ucsd.edu

Locations
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United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92037
Contact: Siddharth Singh    858-246-2352    sis040@ucsd.edu   
Contact       sis040@ucsd.edu   
Principal Investigator: Siddharth Singh, MD         
Sponsors and Collaborators
University of California, San Diego
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Responsible Party: Siddharth Singh, Assistant Professor of Medicine, Division of Gastroenterology, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04721873    
Other Study ID Numbers: 190419
623346 ( Other Grant/Funding Number: Litwin Pioneers in IBD, Crohn's and Colitis Foundation )
First Posted: January 25, 2021    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Weight Loss
Ulcer
Body Weight Changes
Body Weight
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Topiramate
Phentermine
Anticonvulsants
Hypoglycemic Agents
Physiological Effects of Drugs
Central Nervous System Stimulants
Appetite Depressants
Anti-Obesity Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action