Diet, Insulin Sensitivity And the Brain

Obesity Clinical Trial

— DISAB  

Official title:

The Effect of Dietary Patterns and Diet Composition on Insulin Sensitivity and Cerebral Dopamine- and Serotonin Transporters

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297738
• Other study ID #: DISAB
• Status: Completed
• Phase: N/A
• First received: February 16, 2011
• Last updated: January 23, 2013
• Start date: February 2011
• Est. completion date: July 2012

Study information

• Verified date: January 2013
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Obesity and insulin resistance may be in part explained by an altered reward system with changes in the serotonin/dopamine system. These changes might be caused by changes in dietary habits, especially by an increased intake of liquid sugar and an increase in meal frequency. The investigators hypothesize that increasing meal frequency compared to increasing meal size and when consuming a hypercaloric high-sugar diet (HS) compared to a hypercaloric high-fat-high-sugar diet (HFHS) will result in a reduction in cerebral serotonin and dopamine transporters and in a more prominent increase in insulin resistance. In addition, the investigators hypothesize that the changes in insulin sensitivity will be independent of changes in abdominal (visceral) and liver fat and that changes in insulin sensitivity due to the dietary manipulation will co-occur with changes in insulin signaling pathways in peripheral fat and muscle tissue.

Description:

Lean, healthy, young men will follow a hypercaloric HF- or HFHS diet for 6 weeks. Before and after the dietary intervention, the investigators will perform a SPECT-scan for serotonin and dopamine transporters with the radioligand [123I]FP-CIT, administered intravenously. The investigators will also perform a structural MRI for localization. Furthermore the investigators will perform a liver MRS and abdominal MRI for liver fat- and abdominal visceral fat measurement. The investigators will also perform a euglycemic, hyperinsulinemic clamp to measure insulin sensitivity and muscle- and fat biopsies to examine changes in insulin signaling pathways and fat metabolism. After the hypercaloric diet subjects will follow a hypocaloric diet until their weight is back to baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• BMI 19-26 kg/m2

• Age 18-40 years old

• Male gender

• Caucasian

• Stable weight 3 months prior to start study participation

Exclusion Criteria:

• Abnormal oral glucose tolerance test (OGTT)

• Lipid disorders, renal disorders, thyroid disorders, elevated liver enzymes

• Use of medication

• Use of alcohol > 3/day

• Use of ecstasy, amphetamines or cocaine

• Smoking

• History of eating disorder or psychiatric disorder

• Any medical condition, intensive sports ( >3 times/week), shift work

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Obesity

Intervention

Other:
• Meal size increase with HFHS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® with their meals, which results in an increase in meal size.
• Meal size increase with HS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages with their meals, which results in an increase in meal size.
• Meal frequency increase with HFHS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® 3 times a day in between meals, which results in an increase in meal frequency.
• Meal frequency increase with HS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages 3 times a day in between meals, which results in an increase in meal frequency.

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Netherlands Organisation for Scientific Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebral binding of [123I]FP-CIT to serotonin- and dopamine transporters and correlation with changes in in vivo and ex vivo insulin sensitivity	Difference in cerebral binding of the radioligand [123I]FP-CIT to serotonin- and dopamine transporters before and after dietary manipulations and correlation of cerebral dopamine and serotonin transporter binding with changes in in vivo and ex vivo insulin sensitivity.	At baseline and after 6 weeks of hypercaloric HFHS or HS diet	No
Secondary	Abdominal fat mass	Changes in accumulated amount of abdominal (visceral) and liver fat	At baseline and after 6 weeks of HFHS or HS hypercaloric diet	No
Secondary	Glucoregularoty hormones	Changes in glucoregulatory hormones such as glucagon and leptin	At baseline and after 6 weeks of hypercaloric HFHS- or HS diet	No
Secondary	Insulin signalling pathways	Changes in insulin signalling pathways in peripheral fat and muscle tissue	At baseline and after 6 weeks of hypercaloric HFHS- or HS diet	No