Effect of Pancreatic Polypeptide on Gastric Motor Function and Food Intake in Humans

Sponsor

Universitaire Ziekenhuizen Leuven (Other)

Overall Status

Completed

CT.gov ID

NCT03854708

Collaborator

(none)

Enrollment

Location

Arms

6.2

Actual Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators want to observe whether different doses of pancreatic polypeptide infusions influence gastric accommodation (measured as intragastric pressure changes during a liquid meal infusion), gastric emptying and food intake.

Condition or Disease	Intervention/Treatment	Phase
Hunger	Drug: 3 pmol/kgmin pancreatic polypeptide Drug: 10 pmol/kgmin pancreatic polypeptide Drug: Placebo	Phase 4

Detailed Description

As pancreatic polypeptide (PP) influences food behavior in humans, our research group suggests a role via the the gastric accommodation or gastric emptying. Twelve healthy volunteers participated in this single blind, placebo-controlled, crossover trial. An infusion catheter and a manometry probe were positioned in the stomach. After a 15 min stabilization period, saline (placebo), PP 3 pmol/kgmin or PP 10 pmol/kgmin were intravenously infused. Thirty min after the condition, an intragastric nutrient drink (ND) infusion (60 ml/min) started until the volunteer felt maximal satiated. GE was evaluated using the 13C breath test during the 6 hours following the ND infusion. Satiation and hunger were scored on a visual analog scale every 5 minutes.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Effect of Pancreatic Polypeptide on Intragastric Pressure and Satiety During Nutrient Drink Infusion

Actual Study Start Date :

Aug 31, 2010

Actual Primary Completion Date :

Mar 8, 2011

Actual Study Completion Date :

Mar 8, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3 pmol/kgmin pancreatic polypeptide 3 pmol/kgmin of pancreatic polypeptide was intravenously infused.	Drug: *3 pmol/kgmin pancreatic polypeptide** PP 3 pmol/kg*min was intravenously infused 30 minutes before the meal until the end of the meal. For this purpose, a cannula was inserted into the subjects' forearm vein. Human PP (CS Bio, Menlo Park, USA) was dissolved in a 0.9 % saline solution containing 5 % albumin to reduce absorption of PP to the syringe and tubing. Other Names: Pancreatic polypeptide
Experimental: 10 pmol/kgmin pancreatic polypeptide 10 pmol/kgmin of pancreatic polypeptide was intravenously infused.	Drug: *10 pmol/kgmin pancreatic polypeptide** PP 10 pmol/kg*min was intravenously infused 30 minutes before the meal until the end of the meal. For this purpose, a cannula was inserted into the subjects' forearm vein. Human PP (CS Bio, Menlo Park, USA) was dissolved in a 0.9 % saline solution containing 5 % albumin to reduce absorption of PP to the syringe and tubing. Other Names: Pancreatic polypeptide
Placebo Comparator: Placebo 0.9 % saline solution was intravenously infused.	Drug: Placebo Placebo (saline solution) was intravenously infused 30 minutes before the meal until the end of the meal. For this purpose, a cannula was inserted into the subjects' forearm vein. The placebo consists of a 0.9 % saline solution containing 5 % albumin.

Arm

Intervention/Treatment

Experimental: 3 pmol/kg*min pancreatic polypeptide

3 pmol/kg*min of pancreatic polypeptide was intravenously infused.

Drug: 3 pmol/kg*min pancreatic polypeptide

PP 3 pmol/kg*min was intravenously infused 30 minutes before the meal until the end of the meal. For this purpose, a cannula was inserted into the subjects' forearm vein. Human PP (CS Bio, Menlo Park, USA) was dissolved in a 0.9 % saline solution containing 5 % albumin to reduce absorption of PP to the syringe and tubing.

Other Names:

Pancreatic polypeptide

Experimental: 10 pmol/kg*min pancreatic polypeptide

10 pmol/kg*min of pancreatic polypeptide was intravenously infused.

Drug: 10 pmol/kg*min pancreatic polypeptide

PP 10 pmol/kg*min was intravenously infused 30 minutes before the meal until the end of the meal. For this purpose, a cannula was inserted into the subjects' forearm vein. Human PP (CS Bio, Menlo Park, USA) was dissolved in a 0.9 % saline solution containing 5 % albumin to reduce absorption of PP to the syringe and tubing.

Other Names:

Pancreatic polypeptide

Placebo Comparator: Placebo

0.9 % saline solution was intravenously infused.

Drug: Placebo

Placebo (saline solution) was intravenously infused 30 minutes before the meal until the end of the meal. For this purpose, a cannula was inserted into the subjects' forearm vein. The placebo consists of a 0.9 % saline solution containing 5 % albumin.

Outcome Measures

Primary Outcome Measures

The effect of different doses of pancreatic polypeptide infusion on the gastric accommodation (intragastric pressure drop) after nutrient drink infusion. [Until 2 hours after the start of the liquid meal. Liquid meal started 30 minutes after pancreatic peptide dose or placebo iv infusion.]
Intragastric pressure measurements were assessed using a 36-channel high-resolution solid-state manometry probe. After nutrient drink infusion, the intragastric pressure drops to a minimum value (Nadir), which is a measurement for gastric accommodation, and the pressure restores after. The time point of reaching the Nadir is different between subjects, but pressure is measured until 2 hours after nutrient drink to assess the drop.

Secondary Outcome Measures

The effect of different doses of pancreatic polypeptide infusion on nutrient tolerance. [Infusion of the liquid meal ends after 20 minutes or earlier if max satiation is reached by the subjects.]
Liquid nutrient drink was infused at a constant speed of 60 ml/min. At 1-min intervals subjects were asked to score their satiation using a graphic rating scale that combines verbal descriptors on a scale graded from 0 to 5 (0 is threshold, 5 is maximal satiation. Infusion stopped when the subject reached maximal satiation. The time of infusion is a measurement of their nutrient tolerance.
The effect of different doses of pancreatic polypeptide infusion on gastric emptying rate. [Breath samples were collected in exetainers, twice before and every 15 min after the meal until 6 hours thereafter.]
Gastric emptying rate after placebo and PP 10 pmol/kg*min administration was quantified using the breath test. 13C-labeled sodium octanoate were added to the ND (200 mg/L) and emptying of the stomach was assessed by analysis of the exhaled 13CO2.
The effect of different doses of pancreatic polypeptide infusion on satiety and return of hunger. [Satiety and hunger were scored twice before and every 15 min after the meal until 6 hours thereafter.]
The subjects rate their feeling of satiety (in fasted state)/satiation (in fed state) and hunger using a 100 mm line ranging from 0 to 100, as a response on the questions: 'How hungry do you feel? ' and 'How satisfied do you feel?'. 0 means 'not at all', and 100 means 'extremely much'. These feelings cannot be considered to have a better or worse outcome. One expect to have higher hunger and lower satiety scores in fasted state and lower hunger and higher satiation scores in the fed state.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject is between 18 and 65 years of age.
Women of child-bearing potential agree to apply during the entire duration of the trial a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, or some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses.
Subject understands the study procedures and agrees to participate in the study by giving written informed consent.

Exclusion Criteria:

Subject is under age of legal consent, pregnant or breastfeeding.
Subject has current symptoms or a history of gastrointestinal or other significant somatic or psychiatric diseases or drug allergies.
Subject has a significant heart, lung, liver or kidney disease.
Subject has any history of a neurological disorder. Subject has a history of abdominal surgery. Those having undergone a simple appendectomy more than 1 year prior to the screening visit may participate.
History or current use of drugs that can affect glycaemia, gastrointestinal function, motility or sensitivity or gastric acidity.
History or current use of centrally acting medication, including antidepressants, antipsychotics and/or benzodiazepines (in the last year before screening visit).
Subject consumes excessive amounts of alcohol, defined as >14 units per week for females and > 21 units per week for males.
Subject is currently (defined as within approximately 1 year of the screening visit) a regular or irregular user (including "recreational use") of any illicit drugs (including marijuana) or has a history of drug (including alcohol) abuse. Further, patient is unwilling to refrain from the use of drugs during this study.
High caffeine intake (> 500 ml coffee daily or equivalent).
Inability or unwillingness to perform all of the study procedures, or the subject is considered unsuitable in any way by the principal investigator.
Recent participation (<30 days) or simultaneous participation in another clinical study.
Subjects with lactose intolerance.