氟西汀治疗难治性便秘的评价 (REFLECT)

实验性的：氟西汀治疗组

药品：Fluoxetine

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

安慰剂比较：安慰剂对照组

药品：Placebo

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).

不良事件的发生率

在研究期间，每个治疗组中遇到不良事件的参与者的比例。

每周达到≥3csbm的参与者比例

在12周的治疗期间，每周至少要达到3个完全自发的排便（CSBM）的参与者百分比。

与基线相比，SBM的变化在12周的治疗期内

是指过去24小时内发生的肠道运动，而无需使用救援药物或任何其他辅助方法（例如，泻药，灌肠，灌肠，栓剂或数字操纵），包括CSBM

每周CSBM频率的基线变化

与基线相比，每周完全自发的排便（CSBM）的平均变化。

与基线相比

0 =无困难；

1. =轻度难度，需要紧张；
2. =中度难度，需要紧张；
3. =严重的困难，需要紧张的紧张。

与基线相比，SBM平均粪便一致性得分的变化

参与者将使用Bristol凳子表量表自我报告每个SBM的粪便一致性

从基线到治疗期结束的KESS得分的变化

旨在量化慢性便秘的严重程度和症状特征的经过验证的问卷。 它由11个项目组成，每个项目都根据症状严重程度从0到4分。 较高的总分数表明更严重的便秘症状。

PAC-QOL自我评估得分从基线变化

经过验证的特定于便秘的生活质量工具，以评估便秘对日常生活的影响。 它包括28个涵盖四个领域的项目：身体不适，社会心理不适，担心和关注以及满意度，反映了过去两周便秘的影响。

从基线到治疗期结束的GAD-7分数的变化

从基线到第12周的广义焦虑症7（GAD-7）得分的变化，评估焦虑症状。

从基线到治疗期结束的PHQ-9分数的变化

从基线到第12周的患者健康问卷调查表9（PHQ-9）的变化，评估抑郁症状。

从基线到治疗期结束的PHQ-15分数的变化

从基线到第12周的患者健康问卷15（PHQ-15）的变化，评估了与SSD相关的躯体症状严重程度。

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.

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

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).

Proportion of sustained CSBM responders

Percentage of participants achieving ≥3 CSBM per week for ≥4 consecutive weeks during the 12-week treatment period.

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).

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).

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).