Version History

Document evolution from initial concept to final design

Proposal Evolution
Track changes across 14 versions
v1
2024-12-10

V1

Initial 3-partner design with DIT focus

v2
2024-12-11

V2

Added ECS integration, 4 partners

v3
2024-12-12

V3

Budget optimization, equal cohorts

v4
2024-12-13

V4

Added DLW subgroup, 4-partner consortium

v5
2024-12-14

V5

Removed DLW, increased sample size to n=120

v6
2024-12-15

V6

Removed DLW subgroup, streamlined design

v7
2024-12-16

V7

Two-study translational design (human + mouse), added Moro

v8
2024-12-17

V8

Clarified outcome hierarchy (DIT primary)

v9
2024-12-17

V9

Corrected primary objective

v10
2024-12-17

V10

Primary objective DIT only

v11
2024-12-17

V11

Abstract rewrite, flattened secondary hierarchy

v12
2024-12-18

V12

GLP-1 only, expanded biomarkers, mouse strains, wearables

v13
2024-12-21

V13

Corrected hypothesis (low DIT = less weight loss), sex-based stratification (60M/60F), added 9-month visit, diabetes exclusion

v14Current
2024-12-21

V14

MAJOR UPDATE: BodPod+BIA at all visits, MRI with AMRA Medical (baseline+M12), muscle function tests, LPMT at M12, 18-month phone follow-up, detailed mouse experiments with individual timelines per strain

Key Changes Summary
v1 → v2

Added endocannabinoid system (ECS) integration based on Prof. Dalle's expertise

v3 → v4

Expanded consortium to 4 partners with Maastricht University (Prof. Plasqui)

v4 → v5

Removed invasive procedures (BAT imaging, biopsies) based on Guillermo's feedback

v5 → v6

Finalized streamlined observational design with n=120

Design Evolution
v1-v3
Mechanistic subgroup with BAT + Biopsies
v4
Added DLW validation subgroup
v5
Removed invasive procedures, added metabolic flexibility
v6
Final: Pure observational, n=120, no subgroups
Version Comparison
Featurev1v4v6 (Final)
Sample Sizen=96n=96n=120
Partners344
BAT ImagingRemoved
Muscle BiopsiesRemoved
DLW Validation-Removed
Metabolic Flexibility--Added
ECS Profiling-
Discussion: Version History

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