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

Primary Purpose

Colitis, Ulcerative, Obesity

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Phentermine-Topiramate

Placebo

About this trial

This is an interventional treatment trial for Colitis, Ulcerative

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

University of California San DiegoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Weight loss - 5%

Proportion of patients with ≥5% weight loss over baseline

Secondary Outcome Measures

Weight loss - 10%

Proportion of patients with ≥10% weight loss over baseline

Absolute weight loss

Absolute weight loss from baseline

Discontinuation

Discontinuation of therapy due to treatment-related adverse events

Corticosteroid-free clinical remission

PRO2 remission, with no prednisone use within 1 week of assessment

Biochemical remission

Fecal calprotectin (FC) ≤50μg/g

Full Information

NCT ID

NCT04721873

First Posted

January 19, 2021

Last Updated

May 12, 2023

Sponsor

University of California, San Diego

1. Study Identification

Unique Protocol Identification Number

NCT04721873

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 18, 2020 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Diego

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colitis, Ulcerative, Obesity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Phentermine-Topiramate

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo, titrated as active intervention

Primary Outcome Measure Information:

Title

Weight loss - 5%

Description

Proportion of patients with ≥5% weight loss over baseline

Time Frame

22 weeks

Secondary Outcome Measure Information:

Title

Weight loss - 10%

Description

Proportion of patients with ≥10% weight loss over baseline

Time Frame

22 weeks

Title

Absolute weight loss

Description

Absolute weight loss from baseline

Time Frame

22 weeks

Title

Discontinuation

Description

Discontinuation of therapy due to treatment-related adverse events

Time Frame

22 weeks

Title

Corticosteroid-free clinical remission

Description

PRO2 remission, with no prednisone use within 1 week of assessment

Time Frame

22 weeks

Title

Biochemical remission

Description

Fecal calprotectin (FC) ≤50μg/g

Time Frame

22 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Siddharth Singh, MD

Phone

8582462352

sis040@ucsd.edu

Facility Information:

Facility Name

University of California San Diego

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Siddharth Singh

Phone

858-246-2352

sis040@ucsd.edu

Ext

Singh

sis040@ucsd.edu

First Name & Middle Initial & Last Name & Degree

Siddharth Singh, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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