Effect of Intranasal Insulin on Cognitive Processes and Appetite

• ClinicalTrials.gov Identifier: NCT03632681
• Recruitment Status: Completed
• First Posted: August 15, 2018
• Last Update Posted: May 2, 2019
• Sponsor: University of Birmingham
• Collaborator: Queen Elizabeth Hospital NHS Foundation Trust
• Information provided by (Responsible Party): University of Birmingham

Study Description

Brief Summary:

This study investigates the effect of intranasal insulin on cognitive processes (behavioural and neural) in healthy lean and obese female adults. All subjects will receive a single-dose of intranasal insulin and/or placebo (on different days) before participating in several cognitive tasks.

Condition or disease	Intervention/treatment	Phase
Obesity	Drug: Intranasal Insulin; Drug: Intranasal Placebo	Not Applicable

Detailed Description:

It is well established that eating behaviour is affected by metabolic signals (e.g. insulin, ghrelin, serotonin) and is also modulated via food reward processes. However, in humans, eating behaviour is a complex process, which involves habits, long-term goals and social interaction. Thus, recently it has been proposed that higher cognitive processes such as inhibitory control, attention and memory also modulate eating.

Insulin seems to be involved in both metabolic processes and cognitive processes. In the last decade it has been shown that intranasal administration of insulin decreases food intake, especially in women, and enhances thermogenesis and memory. In addition intranasal insulin administration has been shown to affect brain areas related to homeostatic control, reward and memory.

In the proposed study the investigators will examine the effect of intranasal insulin administration on eating, and on metabolic, reward and cognitive processes and their potential interplay. The investigators will also study the effect of body weight on the actions of insulin on these processes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Interactions Between Metabolic, Cognitive and Reward Processes in Appetite - Effects of Intranasal Administration of Insulin
• Actual Study Start Date: April 23, 2018
• Actual Primary Completion Date: April 1, 2019
• Actual Study Completion Date: April 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Insulin; In this arm a single-dose of (160 IU/1.6ml) intranasal insulin will be administrated	Drug: Intranasal Insulin; Intranasal insulin; Other Names: Insulin; Actrapid
Placebo Comparator: Placebo; In this arm a single-dose intranasal placebo will be administrated	Drug: Intranasal Placebo; Intranasal placebo manufactured to mimic smell of insulin; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. fMRI brain response during inhibition to a food stimuli [ Time Frame: 14 minutes ]
   Neural activation during correct inhibition food vs. non-food stimuli trail. Comparing the brain response when subjects correctly withhold for food vs a sports item.

Secondary Outcome Measures :

1. Delay discount of food reward [ Time Frame: 5 minutes ]
   Area under the curve for delay of choosing a food item. Subjects have to choice between a certain amount of food now, or more (which varies between 1-20 pieces) food later (which will vary from 1 hour to 1 year).
2. Delay discount of money reward [ Time Frame: 5 minutes ]
   Area under the curve for delay of choosing a amount of money. Subjects have to choice between a certain amount of money now, or more (which varies between 1-100 pound) money later (which will vary from 1 day, 1 months and 1 year).
3. fMRI brain activity in food picture task [ Time Frame: 18 minutes ]
   Brain responses for food stimuli compared to non-food stimuli. The researchers will measure this by showing subjects food and non-food images while preforming and fMRI-scan and subtract activity during non-food images from the activity pattern when looking at food images.
4. Recall pictures [ Time Frame: 5 minutes ]
   Recall accuracy. The researchers will count the correct amount of pictures remembered in this task and calculate % of pictures remembered in total, and differentiate between the three categories (high caloric/low caloric/control)
5. Recall words [ Time Frame: 10 minutes ]
   Recall words. The researcher will count the correct amount of words remembered in this task
6. Emotional categorisation [ Time Frame: 10 minutes ]
   Accuracy of category and reaction time will be measured for dislike or like words
7. Emotional recall part 1 [ Time Frame: 4 minutes ]
   Recall words of liked and disliked words will be recorded in ECAT
8. Emotional recall part 1 [ Time Frame: 10 minutes ]
   Accuracy of previous exposed or not exposed words will be measured
9. Cookie intake [ Time Frame: 10 minutes ]
   Amount (kcal and gram) of cookies eaten will be measured
10. fMRI neural network during inhibition to a food stimuli [ Time Frame: 14 minutes ]
    Functional connectivity during correct inhibition food vs. non-food stimuli trail.
11. fMRI brain responses during inhibition [ Time Frame: 14 minutes ]
    Neural activation correct No-Go vs. Go trail. Subjects neural activation when they are instructed to go (press) when seeing toiletry or stationary items and react correctly compared to when subjects are instructed not to go (no press) when seeing a food or sport and withhold correctly

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: based on self-representation of gender identity
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy female subjects
• Age 18-65 years at start of the study
• Body Mass Index (BMI) between 18 and 25 kg/m2 for the lean group and between 30 and 40 kg/m2 for the obese group
• Right-handedness (including left-handers could bias the results because of the laterality of brain functions)
• Ability to give informed consent
• Fluent English speaking
• Willingness to be informed about chance findings of pathology

Exclusion Criteria:

• Subjects who have a non-removable metal object in or at their body, such as, for example: Heart pace-maker, artificial heart valve, metal prosthesis, implants or splinters, non-removable dental braces
• Tattoos, that are older than 15 years
• Claustrophobia
• Limited temperature perception and/or increased sensitivity to warming of the body
• Pathological hearing ability or an increased sensitivity to loud noises
• Lack of ability to give informed consent
• Operation less than three months ago
• Simultaneous participation in other studies that involve drugs intake or blood spending
• Acute illness or infection during the last 4 weeks
• Cardiovascular disorders (e.g., hypertrophic cardiomyopathy, long QT syndrome)
• Moderate or severe head injury
• Eating disorders
• No metabolic (e.g. metabolic disorder, diabetes, insulin resistance), psychological (e.g. depression) or neurological (e.g. epilepsy, headache disorder, multiple sclerosis, traumatic brain injuries) diseases or medication in relation to these diseases.
• Intake of any medication that can interfere with the drug or measurements.
• Current weight loss regimens, or more then 5kg weight loss in the last 3 months
• Smoking
• Current pregnancy or breastfeeding
• Current or past history of drug or alcohol dependency - alcohol consumption exceeding 12 units a week
• Food allergies (e.g. peanut allergy lactose and gluten intolerance) or vegetarian/vegan diet
• Disliking the study lunch

Contacts and Locations

Locations

United Kingdom

Univerisity of Birmingham

Birmingham, United Kingdom

Sponsors and Collaborators

University of Birmingham

Queen Elizabeth Hospital NHS Foundation Trust

Investigators

• Principal Investigator: Maartje SPetter, PhD; Univerisity of Birmingham

More Information

• Responsible Party: University of Birmingham
• ClinicalTrials.gov Identifier: NCT03632681
• Other Study ID Numbers: RG_17-102
• First Posted: August 15, 2018
• Last Update Posted: May 2, 2019
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The study protocol and data will be shared on Open Science Forum
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: The study protocol will be shared before including the first participant. The data will become available after the last participant has finished the study.
• Access Criteria: All researchers
• URL: https://osf.io

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Birmingham:

Cognitive processes; Reward processes; fMRI; Insulin

Additional relevant MeSH terms:

Insulin; Insulin, Globin Zinc; Hypoglycemic Agents; Physiological Effects of Drugs