A Phase 2 interventional study of Fluoxetine and Placebo in Refractory Constipation, Somatic Symptom Disorder (DSM-5) and Functional Constipation (FC), sponsored by Zhifeng Zhao, PhD. Not yet recruiting. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by Zhifeng Zhao, PhD · Phase 2, Interventional, and Treatment
This single-center, randomized, double-blind, placebo-controlled trial evaluates the efficacy and safety of fluoxetine (40 mg/day) versus placebo in 194 adults with refractory chronic constipation exhibiting Somatic Symptom Disorder (SSD) features diagnosed by SCID-5. After a 2-week screening period, participants are randomized 1:1 to fluoxetine or matching placebo for 12 weeks. The primary endpoint is the proportion of CSBM responders, defined as an increase of ≥1 CSBM per week from baseline in ≥50% of treatment weeks (Weeks 5-12). Key secondary endpoints include weekly SBM/CSBM frequency, Bristol Stool Form Scale, straining score, bloating severity, Patient Global Impression of Change (PGIC, 7-point), and changes in validated PRO scales (SSD-12, PHQ-15, PHQ-9, GAD-7, PAC-QOL, KESS). Mechanistic assessments include resting-state fMRI and high-resolution anorectal manometry (HRAM). Safety is monitored through adverse events, thyroid/liver/renal function tests, and ECG.
1,046 studies on the registry are indexed under Constipation; 161 are open to participants now.
This study's planned enrollment of 194 is above the median of 75 across 884 interventional studies indexed under Constipation.
Browse Constipation studies →Zhifeng Zhao, PhD is the lead sponsor of 3 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Fluoxetine
Drug: Placebo
Participants receive fluoxetine orally after breakfast, starting at 20 mg/day (1 capsule) for the first 7 days. From Day 8, the dose increases to the target of 40 mg/day (2 capsules), maintained through Week 12. If a participant cannot tolerate the 40 mg dose, the dose may be reduced back to 20 mg/day; if 20 mg remains intolerable, the study drug is discontinued and the participant enters safety follow-up. Rescue medications: For participants in both groups who have no bowel movement for 3 consecutive days or experience intolerable symptoms, a two-tier rescue protocol is available: (1) first line: polyethylene glycol 13.7 g orally; (2) second line: glycerin enema if no response to PEG after 24-48 hours. Rescue medication use must be recorded in the bowel movement diary and eCRF (date, time, dose). Rescue medications are distributed at each 4-week visit. Any bowel movement occurring within 24 hours after rescue medication use is classified as non-spontaneous (non-SBM) and excluded from
Participants in the Placebo Control Group receive placebo tablets that are identical in appearance, taste, and packaging to the fluoxetine tablets. They take one placebo tablet orally once daily after breakfast for 12 weeks, following the same schedule as the treatment group to maintain blinding. Rescue medications: For participants in both groups who have no bowel movement for 3 consecutive days or experience intolerable symptoms, a two-tier rescue protocol is available: (1) first line: polyethylene glycol 13.7 g orally; (2) second line: glycerin enema if no response to PEG after 24-48 hours. Rescue medication use must be recorded in the bowel movement diary and eCRF (date, time, dose). Rescue medications are distributed at each 4-week visit. Any bowel movement occurring within 24 hours after rescue medication use is classified as non-spontaneous (non-SBM) and excluded from the CSBM/SBM endpoint calculation.
Efficacy rate of fluoxetine treatment
The primary efficacy endpoint is the proportion (%) of participants who achieve an increase of ≥ 1 complete spontaneous bowel movement (CSBM) per week relative to baseline in at least four of the last eight weeks (Weeks 5-12), a key indicator of therapeutic response in functional constipation (FC).
Time frame: Baseline (Week -2) through the end of Week 12 (treatment period)
Proportion of Participants Achieving ≥3 CSBM per Week
Percentage of participants who achieve at least 3 complete spontaneous bowel movements (CSBM) per week during the 12-week treatment period.
Time frame: baseline and 12-week
Change in the SBM compared to baseline over the 12-week treatment period
Refers to a bowel movement occurring within the past 24 hours without the use of rescue medications or any other adjunctive methods (e.g., laxatives, enemas, suppositories, or digital maneuvers), including CSBM
Time frame: Baseline to Week-12
Change from Baseline in Weekly CSBM Frequency
The mean change in weekly complete spontaneous bowel movements (CSBM) compared to baseline.
Time frame: Baseline to Week-12
Change in the average straining score for SBM over 12 weeks compared to baseline
0 = no difficulty; 1. = mild difficulty, straining required; 2. = moderate difficulty, straining required; 3. = severe difficulty, intense straining required.
Time frame: Baseline to Week-12
Change in the abdominal bloating score compared to baseline over the 12-week treatment period
Abdominal bloating will be assessed using a 5-point ordinal scale: 0 = none; 1. = mild; 2. = moderate; 3. = severe; 4. = very severe.
Time frame: Baseline to Week-12
Change in the average stool consistency score for SBM over 12 weeks compared to baseline
Participants will self-report the stool consistency of each SBM using the Bristol Stool Form Scale
Time frame: Baseline to Week-12
The change in KESS score from baseline to the end of the treatment period
A validated questionnaire designed to quantify the severity and symptom profile of chronic constipation. It consists of 11 items, each scored from 0 to 4 based on symptom severity. Higher total scores indicate more severe constipation symptoms.
Time frame: Baseline to Week-12
Change in PAC-QOL self-assessment scores from baseline
A validated constipation-specific quality of life instrument developed to assess the impact of constipation on daily living. It includes 28 items covering four domains: physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction, reflecting the effect of constipation over the past two weeks.
Time frame: Baseline to Week-12
The change in GAD-7 score from baseline to the end of the treatment period
Change in the Generalized Anxiety Disorder-7 (GAD-7) score from baseline to Week 12, assessing anxiety symptoms.
Time frame: Baseline to Week-12
The change in PHQ-9 score from baseline to the end of the treatment period
Change in the Patient Health Questionnaire-9 (PHQ-9) score from baseline to Week 12, assessing depressive symptoms.
Time frame: Baseline to Week-12
The change in PHQ-15 score from baseline to the end of the treatment period
Change in the Patient Health Questionnaire-15 (PHQ-15) score from baseline to Week 12, assessing somatic symptom severity related to SSD.
Time frame: Baseline to Week-12
Incidence of adverse events
The proportion of participants experiencing adverse events in each treatment group during the study period.
Time frame: Weeks-2-12
Change in Somatic Symptom Disorder-12 (SSD-12) total score from baseline
Change in the SSD-12 total score (range 0-48) from baseline to Week 12, assessing the cognitive, affective, and behavioral aspects of SSD
Time frame: Baseline to Week 12
Patient Global Impression of Change (PGIC)
Proportion of participants rating their overall constipation improvement at Week 12 using a 7-point PGIC scale (1 = very much improved to 7 = very much worse).
Time frame: Week 12
Proportion of sustained CSBM responders
Percentage of participants achieving ≥3 CSBM per week for ≥4 consecutive weeks during the 12-week treatment period.
Time frame: Baseline to Week 12
Proportion of rescue-medication-free days
The percentage of treatment days on which the participant did not use any rescue medication (PEG or glycerin enema).
Time frame: Baseline to Week 12
Change in resting-state fMRI brain activity from baseline
Change from baseline to Week 12 in predefined ROI-based measures: functional connectivity (FC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuations (ALFF).
Time frame: Baseline to Week 12
Change in anorectal manometry (HRAM) parameters from baseline
Change from baseline to Week 12 in high-resolution anorectal manometry parameters: first sensation threshold (mL), urge to defecate threshold (mL), maximum tolerated volume (mL), and rectal compliance (mL/mmHg).
Time frame: Baseline to Week 12
No study locations are listed for this record.
Plan to share: Yes — Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact zhaozhifeng@outlook.com.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
Access criteria: For more information or to submit a request, please contact zhaozhifeng@outlook.com.
Data sharing details ↗ · prsinfo.clinicaltrials.gov
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Fluoxetine
Zhifeng Zhao, PhD