Secretin Activates Human Brown Fat and Induces Satiation.

NCT ID: NCT03290846

Last Updated: 2019-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-02

Study Completion Date

2019-11-30

Brief Summary

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15 healthy males will be studied with PET/CT, using FDG to investigate glucose metabolism, and radiowater to investigate perfusion. One scan will be performed in controlled cold exposure, to see whether subjects have cold activated brown adipose tissue. Two scans will be performed in room temperature conditions, where all subjects are blinded and randomised to receive placebo and secretin hydrochloride. PET/CT scans will be analysed blinded.

20 healthy males will also be studied with fMRI, in order to investigate brain activity responses to appetizing versus bland foods. This study will be conduced on the same patients as the PET/CT study, but additional subjects with same inclusion and exclusion criteria will be recruited. Two fMRI scans will be performed in room temperature conditions, where all subjects are blinded and randomised to receive placebo and secretin hydrochloride. fMRI scans will be analysed blinded.

Detailed Description

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The PET/CT study will consist of 15 healthy, normal weight males, between ages 18-65. A 2-hour oral glucose tolerance test is performed on screening day. Calorimetry data is collected at baseline (resting and fasting) condition.

Three PET/CT scans on three different days will be performed to all 15 study subjects. Radiowater (15O)-H2O is used to study perfusion and FDG ((F18)-FDG) to study glucose metabolism. After radiowater, PET data is collected from the neck area for 6 minutes. After FDG, PET data is collected for 40 minutes on the neck area, 15 minutes on the chest, 15 minutes on the abdomen and 15 minutes on the brain. Calorimetry is collected during the entire scan. Blood samples are collected during scans for metabolites and for a plasma activity curve.

One scan is performed during controlled, cold exposure. This is done to investigate, whether patients have cold activated brown adipose tissue. After this, subjects will undergo two room temperature condition scans on different days, where participants are single-blinded and randomised to receive placebo (saline) or secretin (secretin hydrochloride) infusions. All scans are done in fasting conditions. After subjects have fed at the PET centre, calorimetry data is collected on all days.

A full body MRI will be performed on a separate day with the Dixon-method.

After scanning visits, brown adipose tissue biopsies will be taken from volunteers by a plastic surgeon. These samples are analysed in Munich.

Dynamic scan data is analysed with the Carimas program, using Patlak plot. Analysis is performed blinded. Further statistics analysis is done with SPSS.

The fMRI study will consist of 20 healthy, normal weight males, between ages 18-65. Subjects who underwent PET/CT scanning will be recruited for this study, as well as an additional group of subjects with the same inclusion and exclusion criteria. A 2-hour oral glucose tolerance test is performed on screening day for additional subjcts.

Two fMRI scans are conducted in room temperature after overnight fast on separate days. Subjects are randomized and blinded to receive placebo and secretin hydrochloride on separate days. Data on brain activity while viewing appetizing versus bland food images is collected during scan. After scanning subjects are given a meal and then followed up for two hours. Data on subjective satiety will be collected with a visual analogue scale questionnaire on nine different timepoints during the day: in preprandial, prandial and postprandial conditions.

Functional MRI data is analyzed with Matlab. Analysis is performed blinded. Satiety score is analzed with SPSS.

Conditions

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Obesity

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single blinded randomised study, secretin infusion is given on one day, saline infusion on an other day.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Participants receive drug and placebo infusion without knowing which day is which.

Study Groups

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Secretin study

PET and MRI scannings will be performed twice. Subjects will be given secretin hydrochloride and placebo on separate days. In addition, subjects will undergo cold exposure PET scanning once.

Group Type EXPERIMENTAL

Secretin Human

Intervention Type DRUG

Randomized, single-blinded secretin hydrochloride infusion.

Saline Solution

Intervention Type DRUG

Randomized, single-blinded saline infusion.

Cold exposure

Intervention Type OTHER

All subjects will undergo a cold exposure PET scan.

Interventions

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Secretin Human

Randomized, single-blinded secretin hydrochloride infusion.

Intervention Type DRUG

Saline Solution

Randomized, single-blinded saline infusion.

Intervention Type DRUG

Cold exposure

All subjects will undergo a cold exposure PET scan.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* healthy normal weight

Exclusion Criteria

* cardiovascular disease, diabetes
* smoking
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Technical University of Munich

OTHER

Sponsor Role collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Pirjo Nuutila

Professor, MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pirjo R Nuutila, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Turku UH

Locations

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Turku PET Centre

Turku, , Finland

Site Status

Countries

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Finland

References

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Sun L, Laurila S, Lahesmaa M, Rebelos E, Virtanen KA, Schnabl K, Klingenspor M, Nummenmaa L, Nuutila P. Secretin modulates appetite via brown adipose tissue-brain axis. Eur J Nucl Med Mol Imaging. 2023 May;50(6):1597-1606. doi: 10.1007/s00259-023-06124-4. Epub 2023 Feb 11.

Reference Type DERIVED
PMID: 36764966 (View on PubMed)

Laurila S, Rebelos E, Lahesmaa M, Sun L, Schnabl K, Peltomaa TM, Klen R, U-Din M, Honka MJ, Eskola O, Kirjavainen AK, Nummenmaa L, Klingenspor M, Virtanen KA, Nuutila P. Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function. Am J Physiol Endocrinol Metab. 2022 Jan 1;322(1):E54-E62. doi: 10.1152/ajpendo.00260.2021. Epub 2021 Nov 22.

Reference Type DERIVED
PMID: 34806426 (View on PubMed)

Laurila S, Sun L, Lahesmaa M, Schnabl K, Laitinen K, Klen R, Li Y, Balaz M, Wolfrum C, Steiger K, Niemi T, Taittonen M, U-Din M, Valikangas T, Elo LL, Eskola O, Kirjavainen AK, Nummenmaa L, Virtanen KA, Klingenspor M, Nuutila P. Secretin activates brown fat and induces satiation. Nat Metab. 2021 Jun;3(6):798-809. doi: 10.1038/s42255-021-00409-4. Epub 2021 Jun 21.

Reference Type DERIVED
PMID: 34158656 (View on PubMed)

Other Identifiers

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T153/2016

Identifier Type: -

Identifier Source: org_study_id