What is the mechanism of action of this treatment?

Bile acid sequestrants, such as colesevelam and cholestyramine, work by binding bile acids in the gut, preventing their reabsorption and thereby reducing diarrhea caused by excess bile acids. This is particularly important for patients with conditions like bile acid diarrhea or those who have undergone ileal resection, where bile acid malabsorption is common. By reducing the bile acid concentration in the colon, these agents help to decrease water and electrolyte loss, improving stool consistency and reducing the frequency of diarrhea. This mechanism is crucial for managing symptoms and improving the quality of life for patients suffering from chronic diarrhea related to bile acid malabsorption.

What side effects are associated with this type of intervention?

Bile acid sequestrants like colesevelam and cholestyramine are generally well-tolerated but can cause side effects such as constipation, bloating, and abdominal discomfort. They may also interfere with the absorption of other medications and fat-soluble vitamins, potentially leading to deficiencies. Loperamide, another common treatment for diarrhea, can cause side effects including constipation, dizziness, and, in rare cases, more severe gastrointestinal issues. Overall, while these treatments are effective, patients should be monitored for these potential side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for diarrhea, including bile acid sequestrants like colesevelam and colestipol. These drugs work by binding bile acids in the gut, which can help reduce diarrhea, particularly in conditions like bile acid malabsorption. Other FDA-approved treatments for diarrhea include loperamide, which decreases stool frequency by slowing intestinal transit, and various antibiotics like trimethoprim for bacterial infections such as Shigella dysentery. While colesevelam is being studied for its effects on lenalidomide-associated diarrhea, its efficacy in other types of diarrhea has been documented, showing significant symptom improvement in patients with bile-acid malabsorption.

What other types of research exist?

Promising novel alternatives to Colesevelam for treating diarrhea include cholestyramine, colestipol, cholpor, and quaternized colestipol. Pepto-Bismol, which has shown bile acid sequestration capabilities, may also be considered.

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Bile Acid Sequestrant

Colesevelam for Lenalidomide-Associated Diarrhea in Multiple Myeloma

Phase 2

Waitlist Available

Led By Malin Hultcrantz, MD, PhD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Experiencing grade 1 or more diarrhea according to the CTCAE 5.0 criteria for at least 4 out of 7 days preceding screening and study inclusion

Treatment with single agent lenalidomide maintenance

Must not have

Patients currently already receiving a bile acid sequestrant or have previously used bile acid sequestrant drugs for diarrhea and had no benefit

Patients with history of bowel obstruction

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing colesevelam, a drug usually used to lower cholesterol, to see if it can help reduce diarrhea in multiple myeloma patients taking lenalidomide. These patients often experience diarrhea as a side effect of their treatment. Colesevelam works by attaching to substances in the gut, which can help firm up stools and reduce diarrhea.

Who is the study for?

This trial is for adults over 18 with multiple myeloma on lenalidomide maintenance who are experiencing mild to severe diarrhea. They must be able to follow the study plan and get treatment at Memorial Sloan Kettering Cancer Center. People can't join if they're allergic to colesevelam, have used bile acid sequestrants without relief, have bowel obstruction, very high triglycerides or a history of related pancreatitis, or diarrhea from an infection.

What is being tested?

The trial is testing the safety and effect of colesevelam pills on controlling diarrhea caused by lenalidomide in multiple myeloma patients. It aims to see how well colesevelam manages this side effect during their maintenance therapy.

What are the potential side effects?

Colesevelam may cause side effects such as constipation, indigestion, nausea, increased triglycerides levels and possible hypersensitivity reactions in those allergic to its components.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had diarrhea for at least 4 days in the past week.

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I am currently on lenalidomide maintenance therapy alone.

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I am 18 years old or older.

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I am scheduled for lenalidomide treatment at MSK.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have used bile acid drugs for diarrhea without any improvement.

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I have had a blockage in my intestines before.

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I have had pancreatitis caused by high triglyceride levels.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Improvement of lenalidomide-associated diarrhea evaluated by CTCAE 5.0

Secondary study objectives

GI symptom assessment

Side effects data

From 2010 Phase 4 trial • 42 Patients • NCT01122108

Gas

Diarrhea

Mild Indigestion

Bloating

Increased Urination

Abdominal Cramps

Belching

Intermittent R Back Thigh Pain

Moderate Indigestion

Severe Indigestion

Headache

Moderate Nausea

Vomitting

100%

80%

60%

40%

20%

Study treatment Arm

More Than 30 Minutes After Last Beverage

Cholestyramine (12g)

Colesevelam HCl (3.75 Grams)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Participants with MyelomaExperimental Treatment1 Intervention

Individuals with Myeloma on lenalidomide maintenance who experience grade 2 or more diarrhea

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Colesevelam Pill

2018

Completed Phase 2

~30

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Bile acid sequestrants, such as colesevelam and cholestyramine, work by binding bile acids in the gut, preventing their reabsorption and thereby reducing diarrhea caused by excess bile acids. This is particularly important for patients with conditions like bile acid diarrhea or those who have undergone ileal resection, where bile acid malabsorption is common. By reducing the bile acid concentration in the colon, these agents help to decrease water and electrolyte loss, improving stool consistency and reducing the frequency of diarrhea. This mechanism is crucial for managing symptoms and improving the quality of life for patients suffering from chronic diarrhea related to bile acid malabsorption.

Double-blind trial of cholestyramine in post-vagotomy diarrhoea.Oral cholestyramine and paregoric therapy for intractable diarrhea following surgical correction of catastrophic disease of the GI tract in neonates.Bile acids in the diarrhoea of ileal resection.