Pharmacotherapy, Slow Transit Constipation
Conditions
Keywords
Slow Transit Constipation, Lubiprostone, Polyethylene Glycol, Randomized Controlled Trial, medication
Brief summary
Lubiprostone has established efficacy and a favorable safety profile in chronic constipation and irritable bowel syndrome with constipation (IBS-C). However, clinical data specifically supporting its use in slow-transit constipation (STC), a distinct subtype of chronic constipation, remains limited.
Detailed description
Slow-transit constipation (STC) is a common subtype of chronic constipation, accounting for up to 30% of cases. Its clinical hallmarks include a diminished or absent urge to defecate and a significantly reduced stool frequency (spontaneous bowel movements \<3 per week). The condition often follows a prolonged and progressively worsening course, characterized by straining, passage of hard stools, and associated symptoms such as abdominal pain and bloating. In severe cases, fecal impaction and consequent colonic obstruction may occur, substantially impairing the patient's quality of life. Non-surgical management, including lifestyle modifications, pharmacological therapy, gut microbiome modulation, and sacral nerve stimulation, remains the first-line approach for most STC patients. Among these, pharmacotherapy is central. Conventional agents include bulk-forming, osmotic, and stimulant laxatives, as well as prokinetics. However, these options are often limited by adverse effects-such as abdominal pain, bloating, rash, drug dependence, malabsorption, and electrolyte imbalances-and the development of tolerance with long-term use. This frequently leaves patients with inadequate relief, creating an urgent need for more effective and safer therapeutics. Lubiprostone, a chloride channel activator that functions as a secretagogue, enhances intestinal fluid secretion and motility. Its efficacy and safety in chronic idiopathic constipation and irritable bowel syndrome with constipation are well-documented, leading to approvals by the U.S. FDA for these indications. Nevertheless, specific data on its use for STC, a distinct pathophysiological entity, is lacking. This study is therefore designed to evaluate the clinical efficacy and safety of lubiprostone in an STC population, with the aim of generating new evidence to inform precise treatment strategies for this condition.
Interventions
DRUGLubiprostone
Patients were instructed to orally ingest Lubiprostone Soft Capsules (provided by Nanjing Chia-Tai Tianqing Pharmaceutical Company) at a dose of 24 μg twice daily with food and water during breakfast and dinner. The capsules must be swallowed whole without splitting or chewing. The treatment duration was 4 weeks, and medication adherence was monitored through patient diaries and pill count of returned medication.
DRUGPolyethylene glycol (PEG )
Subjects in the control group will receive the standard treatment of polyethylene glycol 4000 powder at a dosage of 10 g, twice daily. Each dose will be dissolved in 200-250 mL of water and administered orally for 4 weeks.
Sponsors
Third Military Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients voluntarily participated in the study and provided signed informed consent; 2. Met the Rome IV diagnostic criteria for functional constipation; 3. Had fewer than 3 spontaneous bowel movements (SBMs) per week; 4. More than 20% the radio-paque markers localized in the colon after 72 hours based on colonic transit studies; 5. Were able to complete the bowel movement diary and study questionnaires as required by the study protocol; 6. Agreed to use effective contraception from the time of signing the informed consent form until 3 months after the last dose of the study drug; 7. Aged 18 years or older, both males and females.
Exclusion criteria
1. Pregnant or lactating women. 2. Patients with severe outlet obstruction constipation (e.g. Oxford Grade IV or above for rectal prolapse, rectocele \> 3.1 cm, puborectalis syndrome). 3. Patients with hyperthyroidism or hypothyroidism. 4. Patients with opioid-induced constipation. 5. Patients with megacolon or megarectum. 6. Patients with apparent mechanical intestinal obstruction. 7. Patients with inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis). 8. Patients with malignant tumors of the digestive system. 9. Patients with a history of colorectal surgery. 10. Patients with a previous history of taking lubiprostone. 11. Patients with severe symptoms of depression or anxiety. 12. Patients with known or suspected hypersensitivity to lubiprostone/polyethylene glycol 4000 or any excipients. 13. Patients requiring medications for Parkinson's disease, antipsychotics, antimanic agents, or psychostimulants. 14. Patients with severe cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurological, or psychiatric diseases. 15. Other patients deemed by the investigator as unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in spontaneous bowel movements (SBMs) frequency from baseline during the first week | From 2 weeks prior to the first dose through 4 weeks after treatment initiation | The change from baseline in the weekly average number of SBMs reported during the first week after treatment initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The percentage of patients with SBMs within 24 hours after the first intake of the study drug | Day 1 after treatment initiation | — |
| Time to first SBM occurrence after treatment initiation | Up to 4 weeks after treatment initiation | — |
| The percentage of patients reporting 3 or more SBMs/wk | From 2 weeks prior to the first dose through 4 weeks after treatment initiation | — |
| The percentage of patients achieving an increase of ≥1 SBMs/week from baseline | From 2 weeks prior to the first dose through 4 weeks after treatment initiation | — |
| The change from baseline in the weekly average number of SBMs at weeks 2, 3, and 4 | From 2 weeks prior to the first dose through 4 weeks after treatment initiation | — |
| The change from baseline in the Bristol Stool Form Scale (BSFS) values for SBMs at weeks 1 and 4 | The 1 and 4-week treatment period has been completed | The BSFS values can be described as the following 7 types: 1. separate hard lumps; 2. sausage-shaped but lumpy; 3. like a sausage but with cracks; 4. like a sausage, smooth and soft; 5. soft blobs with clear cut edges; 6. a mushy stool; and 7. watery. |
| The change from baseline in the ratings of straining associated with SBMs at weeks 1 and 4 | The 1 and 4-week treatment period has been completed | The ratings of straining will be described using a 5-point Likert scale: 0= absent; 1= mild; 2= moderate; 3= severe; and 4= very severe |
| The change from baseline in the Wexner constipation score at weeks 1 and 4 | The 1 and 4-week treatment period has been completed | The Wexner Constipation Score will be recorded in terms of scores. Questions examine constipation in its clinical expressions. Each question is answered on a scale of 0 to 4. The scale ranges from 0 (best) to 30 (worst) |
| The change from baseline in the Patient Assessment of Constipation Quality of Life (PAC-QOL) score at weeks 1 and 4 | The 1 and 4-week treatment period has been completed | The full PAC-QOL consists of 28 items rated on a 5-point Likert scale ("1" = Not at all / None of the time; "2" = A little bit / A little of the time; "3" = Moderately /Some of the time; "4" = Quite a bit / Most of the time; "5" = Extremely / All of the time) |
| The patients' satisfaction scores at weeks 1 and 4 | The 1 and 4-week treatment period has been completed | The patients' satisfaction scores will be described using a 5-point Likert scale: 0= Not at all; 1= A little bit; 2= Moderately; 3= Quite a bit; and 4= Extremely |
| The rate of adverse reactions, including nausea, diarrhea, and abdominal pain. | Up to 4 weeks after treatment initiation | — |
Countries
China
Contacts
CONTACTyansen Huang, MS
STUDY_DIRECTORWeidong Tong, MD
Army Medical Center (Daping Hospital)
Outcome results
None listed