Constipation Treatment for Chronic Kidney Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Tennessee
Must not be taking: Antibiotics, Immunosuppressants, Prebiotics, Probiotics
Disqualifiers: Drug abuse, IBS, Liver cirrhosis, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Constipation is one of the most prevalent gastrointestinal disorders in patients with chronic kidney disease (CKD) and has been associated with their adverse kidney and cardiovascular outcomes; however, little is known about the effects of constipation treatment on clinical outcomes nor on outcome-related biochemical and microbiological parameters in patients with CKD. The investigators aim to test the feasibility of delivering an intervention with constipation treatment and determine its effects on changes in clinical, biochemical, and microbiological parameters in patients with CKD and constipation.
Will I have to stop taking my current medications?
The trial requires that you stop taking any laxatives for at least one week before screening, but you can use one bisacodyl 5 mg tablet if you don't have a bowel movement for 3 days or if symptoms become intolerable. Also, you must not have used antibiotics, immunosuppressants, prebiotics, or probiotics within 30 days before joining the study.
What data supports the effectiveness of the drug Linaclotide (Linzess, Constella) for treating constipation in patients with chronic kidney disease?
Linaclotide, a secretagogue, has been shown to be effective in treating chronic idiopathic constipation (CIC) in patients who do not respond to other treatments, according to guidelines reviewed in a study. This suggests it may also help with constipation in chronic kidney disease, although direct evidence for this specific condition is not provided.
12345How is the drug Linaclotide unique for treating constipation in chronic kidney disease?
Linzess (Linaclotide) is unique because it has very limited systemic absorption, making it safe for patients with chronic kidney disease (CKD), and it works by increasing fluid secretion in the intestines to help ease constipation.
678910Eligibility Criteria
This trial is for adults over 18 with chronic kidney disease stages G3-G5 who are not on dialysis, have an eGFR under 60 mL/min/1.73m2, and suffer from functional or opioid-induced constipation. Participants must stop taking laxatives a week before the study but can use a rescue tablet if needed. Women must test negative for pregnancy unless postmenopausal or surgically sterile.Inclusion Criteria
Patients able and willing to provide written informed consent and HIPAA authorization
I am not pregnant, or I am postmenopausal, or I have had a tubal ligation or hysterectomy.
I have constipation as defined by specific medical criteria.
+9 more
Exclusion Criteria
I have galactosemia.
I have liver cirrhosis or chronic active hepatitis, but treated hepatitis is okay.
I have had surgery on my digestive system, but not for appendicitis.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2 weeks
Treatment
Participants receive a 4-week intervention of constipation treatment with lactulose
4 weeks
Weekly visits for monitoring and assessment
Follow-up
Participants are monitored for changes in clinical, biochemical, and microbiological parameters
2 weeks
1-2 visits for follow-up assessments
Participant Groups
The trial is exploring how treating constipation affects people with chronic kidney disease (CKD). It will look at whether this treatment can improve clinical outcomes and influence biochemical and microbiological parameters in patients with CKD who also experience constipation.
2Treatment groups
Experimental Treatment
Active Control
Group I: Constipation treatmentExperimental Treatment1 Intervention
A 4-week intervention of constipation treatment with lactulose
Group II: ControlActive Control1 Intervention
No constipation treatment except bisacodyl rescue therapy
Constipation treatment is already approved in United States, European Union, Canada for the following indications:
πΊπΈ Approved in United States as Linzess for:
- Irritable bowel syndrome with constipation
- Chronic idiopathic constipation
- Functional constipation
πͺπΊ Approved in European Union as Constella for:
- Irritable bowel syndrome with constipation
- Chronic idiopathic constipation
π¨π¦ Approved in Canada as Constella for:
- Irritable bowel syndrome with constipation
- Chronic idiopathic constipation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memphis VA Medical CenterMemphis, TN
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Who Is Running the Clinical Trial?
University of TennesseeLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
University of FloridaCollaborator
References
Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. [2021]Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. It has a great impact on the quality of life and on health care system and represents a heavy economic burden. The diagnosis is based on symptoms, classified by the Rome IV criteria. The aim of this review was to evaluate the current therapeutic guidelines for adult CIC and highlight new emerging treatments. In detail, European, French, Spanish and Korean guidelines have been identified and compared. Osmotic laxatives, and in particular polyethylene glycol, represent the first-line therapeutic approach. Stimulant laxatives are recommended as a second-line therapy. Pelvic floor rehabilitation is recommended in patients with ano-rectal dyssynergia. In patients who fail to improve with pharmacological therapies sacral nerve stimulation is considered as last chance before surgery. Surgical approach has however limited indications in selected cases. Inertia coli refractory to any approach and obstructed defecation are two subtypes which can benefit from surgery. Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available.
Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis. [2021]Pentasa (prolonged-release mesalazine [5-ASA]) has been available for >30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic literature review and meta-analysis was undertaken to provide an up-to-date evaluation of oral Pentasa efficacy and safety for induction and maintenance of remission.
Delivery and fate of oral mesalamine microgranules within the human small intestine. [2019]Oral use of mesalamine in inflammatory bowel disease requires slow-release preparations to prevent premature absorption and inactivation. Resulting luminal concentrations within the human small intestine are unknown. The aim of this study was to determine human intestinal delivery patterns of mesalamine from a microgranule preparation (Pentasa; Ferring Arzeimittel, Kiel, Germany) effective in Crohn's disease with small bowel involvement.
A New Chinese Medicine Intestine Formula Greatly Improves the Effect of Aminosalicylate on Ulcerative Colitis. [2022]Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon. Current medical treatment of UC relies predominantly on the use of traditional drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which failed to effectively control this disease's progression and produced various side effects. Here, we report a new Chinese medicine intestine formula (CIF) which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In the present study, 60 patients with chronic UC were treated with oral mesalazine alone or in combination with CIF enema. The combination of mesalazine and CIF greatly and significantly improved the clinical symptoms and colon mucosal condition and improved the Mayo Clinic Disease Activity Index and health-related quality of life, when compared to mesalazine alone. In particular, the addition of CIF further decreased serum levels of tumor necrosis factor-alpha and hypersensitivity C-reactive protein but in contrast increased interleukin-4. Thus, the results demonstrate the beneficial role of CIF in UC treatment, which may be mediated by the regulation of inflammation.
Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study. [2018]Oral aminosalicylates are well established in the treatment of active mild/moderate ulcerative colitis (UC) when the disease is extensive (that is, beyond the splenic flexure). The majority of clinical symptoms relate to disease activity in the distal part of the colon and therefore this study was designed to investigate if adding a mesalazine enema to oral mesalazine has additional benefit for patients with extensive mild/moderate active UC.
Effect of Lubiprostone on Urinary Protein Excretion: A Report of Two IgA Nephropathy Patients with Chronic Constipation. [2020]Disturbance of the normal gut microbiota has been implicated in the pathogenesis of various diseases, including chronic kidney disease (CKD). A common CKD symptom is chronic constipation. Lubiprostone is a safe and efficacious drug for treating chronic constipation. We herein report 2 patients with IgA nephropathy treated with lubiprostone (24 ΞΌg 1Γ/day). The lubiprostone treatment ameliorated their chronic constipation and, unexpectedly, reduced the urinary protein excretion, urinary liver-type fatty acid binding protein and urine occult blood. These results may indicate that lubiprostone is a useful therapeutic intervention against the progression of IgA nephropathy with chronic constipation.
Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. [2017]When patients complain of recurrent functional bowel disorders consisting of alterations in intestinal transit with abdominal pain or discomfort, treatment is purely symptomatic. Increased intake of dietary fibre or use of a bulk-forming or osmotic laxative is used when constipation is the main complaint. Linaclotide, a small peptide closely related to certain toxins secreted by diarrhoea-causing strains of Escherichia coli, has been authorised in the European Union for the treatment of adults with recurrent functional bowel disorders consisting mainly of constipation. Clinical evaluation of linaclotide includes no trials versus other laxatives. It is based on two placebo-controlled trials including a total of about 1600 patients, lasting 3 and 6 months. A pooled analysis of the results obtained at 3 months showed more frequent "relief" with linaclotide than with placebo. Adverse effects included gastrointestinal disorders, with diarrhoea occurring in one in five patients. Diarrhoea was sometimes severe or prolonged. About 10% of patients discontinued linaclotide because of gastrointestinal adverse effects (diarrhoea in half of these cases). The consequences of diarrhoea can be severe, particularly in patients predisposed to fluid and electrolyte imbalances. Co-administration of other laxative substances enhances the laxative effect of linaclotide. The laxative action is likely to reduce the gastrointestinal absorption of co-administered medications. Linaclotide should be avoided during pregnancy, as there are no relevant safety data. In practice, given the absence of head-to-head comparisons with other laxatives, linaclotide is currently just another laxative with no proven advantages over existing first-line options.
Efficacy of Lactulose versus Senna Plus Ispaghula Husk Among Patients with Pre-Dialysis Chronic Kidney Disease and Constipation: A Randomized Controlled Trial. [2022]Constipation is a common problem among patients with advanced chronic kidney disease (CKD), leading to a loss of quality of life. Pharmacologic treatments are in common use, but whether lactulose and senna plus ispaghula husk is effecive to treat constipation among patients with pre-dialysis CKD remains unknown.
Constipation in Patients With Chronic Kidney Disease. [2023]Constipation is a frequent symptom in patients with chronic kidney disease (CKD). This review outlines the mechanisms and management of constipation in patients with CKD from a physician's perspective. Common causes of constipation in patients with CKD include concomitant medications, low dietary fiber intake, water-restricted diet, lack of physical activity, altered gut microbiota, and reduced gastrointestinal motility. Constipation has a negative impact on overall health, and, in particular, the presence of constipation has been associated with worsening kidney function and increased risk of developing advanced stages of CKD. Although lifestyle and dietary modifications may not always be practical for patients with CKD, they are recommended because they are beneficial as they lower mortality in patients with CKD. The use of laxatives containing magnesium salts, bulking agents, and osmotic laxatives may have insufficient efficacy and may be associated with adverse effects. In contrast, lactulose and lubiprostone have been shown to exhibit reno-protective effects. Linaclotide and plecanatide have very limited systemic absorption and appear safe in patients with CKD. Tenapanor reduces paracellular intestinal phosphate absorption in addition to blocking sodium uptake by enterocytes, and provides additional benefit in patients patients with CKD who have hyperphosphatemia and constipation. Prucalopride leads to improvements in bowel function and constipation-related symptoms in cases in which response to conventional laxatives are inadequate. However, the dose of prucalopride should be reduced to 1 mg once daily for patients with CKD. In conclusion, there are important advances on the impact and treatment of constipation in patients with CKD.
Linaclotide (Linzess) for Irritable Bowel syndrome With Constipation and For Chronic Idiopathic Constipation. [2022]Linaclotide (Linzess) for irritable bowel syndrome with constipation and for chronic idiopathic constipation.