Pilot Study of GCC Agonists to Identify a Cyclic-GMP Signal in Duodenal Tissue of Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 43
- 试验地点
- 4
- 主要终点
- Cyclic guanosine monophosphate (cGMP) levels
研究概览
简要总结
This early phase I trial studies the guanylyl cyclase C (GCC) agonist effect on cGMP signal in duodenal tissue. Plecanatide and linaclotide are drugs approved by the Food and Drug Administration for the treatment of conditions related to constipation. This trial aims to see the effects of taking either one of two drugs, plecanatide or linaclotide, or no drug, on a certain chemical found in the tissue collected from small intestine and how they compare.
详细描述
PRIMARY OBJECTIVE:
I. To assess and compare participants randomly assigned 1:1:1 to one of three intervention arms (plecanatide 3 mg versus linaclotide 145 mcg versus no active agent) with respect to change in cyclic guanosine monophosphate (cGMP) accumulation in normal appearing duodenal mucosa specimens.
SECONDARY OBJECTIVES:
I. Characterization and comparison of the following outcomes (in prioritized order):
Ia. cGMP levels in luminal fluid from participants receiving either linaclotide or plecanatide to fluid from participants receiving no agent; Ib. Vasodilator stimulated phosphoprotein (VASP) phosphorylation in normal-appearing duodenal mucosa biopsy specimens from participants receiving either linaclotide or plecanatide to those specimens from participants receiving no agent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled for clinically indicated esophagogastroduodenoscopy (EGD)
- •Age >= 18 years of age. Note: Because no dosing or adverse event (AE) data are currently available on the use of plecanatide or linaclotide in participants < 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable
- •Willing to provide mandatory biospecimens as specified in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Not pregnant or breastfeeding, as determined by pregnancy test prior to EGD procedure. Note: The effects of plecanatide and linaclotide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 2 weeks after discontinuing study agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Breastfeeding should be discontinued if the mother is treated with plecanatide or linaclotide
- •Ability to understand and the willingness to sign a written informed consent document
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
排除标准
- •Prior treatment in the past week with plecanatide, linaclotide, or other agent whose primary mechanism of action is that of a GCC agonist
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition of plecanatide or linaclotide
- •Use of any other investigational agents =< 12 weeks prior to registration
- •Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements
- •History of gastric bypass, gastric sleeve, or bariatric surgery
研究组 & 干预措施
Arm I (plecanatide, EGD)
Patients receive a single dose of plecanatide (3 mg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Biopsy (Procedure)
Arm I (plecanatide, EGD)
Patients receive a single dose of plecanatide (3 mg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Biospecimen Collection (Procedure)
Arm I (plecanatide, EGD)
Patients receive a single dose of plecanatide (3 mg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Esophagogastroduodenoscopy (Procedure)
Arm I (plecanatide, EGD)
Patients receive a single dose of plecanatide (3 mg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Plecanatide (Drug)
Arm II (linaclotide, EGD)
Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Biopsy (Procedure)
Arm II (linaclotide, EGD)
Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Biospecimen Collection (Procedure)
Arm II (linaclotide, EGD)
Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Esophagogastroduodenoscopy (Procedure)
Arm II (linaclotide, EGD)
Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.
干预措施: Linaclotide (Drug)
Arm III (EGD)
Patients undergo standard of care EGD with biopsy and luminal fluid collection.
干预措施: Biopsy (Procedure)
Arm III (EGD)
Patients undergo standard of care EGD with biopsy and luminal fluid collection.
干预措施: Biospecimen Collection (Procedure)
Arm III (EGD)
Patients undergo standard of care EGD with biopsy and luminal fluid collection.
干预措施: Esophagogastroduodenoscopy (Procedure)
结局指标
主要结局
Cyclic guanosine monophosphate (cGMP) levels
时间窗: Up to 2 years
Will compare cGMP levels measured in normal-appearing duodenal mucosa biopsy specimens from participants receiving linaclotide or plecanatide to cGMP levels in specimens from participants receiving no active treatment. Will evaluate the difference between the control and each treated arm in cGMP levels using two-tailed two-sample Student t-tests. If necessary, a log transformation or Wilcoxon rank-sum will be used, as appropriate.
次要结局
- Vasodilator-stimulated phosphoprotein (VASP) phosphorylation in normal appearing duodenal mucosa(Up to 2 years)
- cGMP levels in luminal fluid(Up to 2 years)