Bromocriptine and Insulin Sensitivity

Insulin Sensitivity Clinical Trial

— BIS  

Official title:

Bromocriptine and Insulin Sensitivity in Lean and Obese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02428946
• Other study ID #: NL49417.018.14 METC 2014/147
• Status: Completed
• Phase: N/A
• First received: October 17, 2014
• Last updated: May 23, 2016
• Start date: October 2014
• Est. completion date: December 2015

Study information

• Verified date: May 2016
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

In this study the investigators will examine the effect of dopamine (bromocriptine) on insulin sensitivity in lean and obese subjects. Furthermore, the investigators will examine whether the timing of bromocriptine administration has influence on insulin sensitivity.

To do so, the investigators will include lean and obese subjects who will use 2 times 2 weeks bromocriptine. In randomized order, they will use it in the morning or in the evening.

The investigators will examine insulin sensitivity by performing a 7-point oral glucose tolerance test.

Furthermore, the investigators will examine energy expenditure and subjects will keep track of their eating behaviour in the 3 days before each study visit.

Description:

Bromocriptine, a dopamine 2 receptor agonist, has recently been approved in the treatment of type 2 diabetes mellitus(DM2). Bromocriptine causes a significant improvement of fasting plasma glucose and Hba1C values. The exact mechanism of action of bromocriptine is still unknown.

Earlier, the investigators performed a study to show the effects of bromocriptine on brown adipose tissue (BAT) activity (the DEBAT study (Medisch Etische Toetsingscommissie) METC nr 2013_107). Namely, BAT, known for its capacity to dissipate excess energy, might have been involved in this process as stimulation by the sympathetic nervous system is the principal driving force in controlling BAT activity. However, the investigators have shown that bromocriptine did not influence BAT activity or energy expenditure in healthy, lean subjects.

The investigators did found an effect of bromocriptine on insulin sensitivity unexpectedly, subjects became significantly less insulin sensitive after bromocriptine use.

Circadian neuroendocrine rhythms, especially the dopaminergic and serotonergic neurotransmitter activity, play a pivotal role in the development of seasonal and non-seasonal changes in body fat stores and insulin sensitivity. Therefore, the timing of bromocriptine administration might be of great importance in changes in insulin sensitivity. Indeed, in the treatment for DM2, a bromocriptine quick release variant is given in the morning. In the former study the investigators instructed the subjects to use the bromocriptine in the evening in combination with the evening meal. The investigators decided to do so because bromocriptine had to be taken in combination with food. The investigators wanted a high level of dopamine just before the 18F-Fludeoxyglucose(18F-FDG) positron emission tomography (PET) computed tomography (CT) scan to get a maximum effect of dopamine on BAT. But the subjects had to be fasted for the OGTT and 18F-FDG-PET-CT scan. Therefore, the investigators decided to give the (long-acting) bromocriptine in the evening.

Also, the effect of bromocriptine might be different in lean or obese subjects. Obesity is associated with an increased sympathetic tonus. Therefore, the baseline condition is different in lean or obese subjects which may cause different effects of bromocriptine treatment.

In this study the investigators aim to investigate whether the timing (e.g. morning or evening) of bromocriptine administration (1,25mg/day during the first week and 2,50mg/day during the second week) has different effects on insulin sensitivity in both lean and obese males.

At visit 1: Informed consent, medical history, vital signs and laboratory measurements will be obtained. The investigators will also perform an oral glucose tolerance test (OGTT), and an energy expenditure(EE) measurement after 60 minutes bed rest.

After visit 1: subjects will start using bromocriptine (1,25mg/day during the first week and 2,50mg/day during the second week) randomization to timing: in the morning or evening.

Visit 2: EE after 60 minutes rest. OGTT. 2 weeks washout period Visit 3: EE after 60 minutes rest. OGTT. After visit 3: start using bromocriptine (1,25mg/day during the first week and 2,50mg/day during the second week) at other time point.

Visit 4: EE after 60 minutes rest. OGTT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Caucasian origin

• Subjects should be able and willing to give informed consent

• BMI range of 19-23 kg/m2 or BMI> 27 kg/2

Exclusion Criteria:

• Renal failure (creatinine>135mmol/l)

• Liver failure (ASAT/ALAT > 3 times higher than the normal upper value)

• Daily use of prescription medication

• Known hypersensitivity to bromocriptine.

• Uncontrolled hypertension

• Known history of coronary artery disease or valvulopathy

• History of severe psychiatric disorders.

• Prolactin-releasing pituitary tumor (prolactinoma).

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Insulin Resistance
• Insulin Sensitivity

Intervention

Drug:
• Bromocriptine
Investigating the randomized order for timing of bromocriptine administration

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Timing of administration of bromocriptine	To determine whether there is a beneficial effect on insulin sensitivity when bromocriptine is given in the morning, as compared to bromocriptine in the evening in Caucasian, lean and obese males	6 weeks	No
Secondary	Difference in insulin sensitivity between lean and obese males before and after the use of bromocriptin	To determine whether there are differential effects of bromocriptine treatment on insulin sensitivity in obese or lean healthy, Caucasian males	6 weeks	No
Secondary	Difference in energy expenditure in lean and obese before and after the use of bromocriptin	To determine whether the difference in timing of bromocriptine influences energy expenditure during thermoneutral conditions in Caucasian, lean and obese males	6 weeks	No