Clinical trial NCT03590496: Safety and Efficacy of Propionate for Reduction of LDL Cholesterol
Official title: Safety and Efficacy of PROPionatE for Reduction of LDL Cholesterol (PROPER-LDL Trial) - A Phase 2 Randomized Placebo Controlled Double-blind Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypercholesterolemia
Keywords: propionate
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2018-07-18
Enrollment: 62
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The objective of the trial is to evaluate a potential impact of food supplements with the short chain fatty acid propionate on blood LDL cholesterol level.

Detailed description: 62 patients with low cardiovascular risk will be 1:1 randomized to receive either placebo (b.i.d.) or 500mg of propionate (b.i.d.). The primary endpoint is the change (delta) in blood LDL cholesterol levels after 8 weeks.

Eligibility criteria: Inclusion Criteria:

* patients with hypercholestrolemia and a LDL serum level of \> 115 mg/dl
* age of patient between 20 and 70 years
* participant is fully competent and has given his/her written informed consent to the scheduled trial conduct

Exclusion Criteria:

* patients with acute coronary syndrome in the last 4 weeks
* patients with chronic symptomatic heart failure (NYHA 2-4)
* patients with chronic renal failure and a GFR \< 45 ml/min
* patients with chronic liver disease
* patients with hematological diseases
* patients with severe diseases of other organ systems (tumors, infections)
* pregnancy

Primary outcomes:
measure: LDL-cholesterol reduction
timeFrame: 8 weeks
Secondary outcomes:
measure: total cholesterol
timeFrame: 8 weeks
measure: HDL-cholesterol
timeFrame: 8 weeks
measure: non HDL
timeFrame: 8 weeks
measure: Ratio HDL/LDL
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Arash Haghikia, PD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, Pais P, Lopez-Jaramillo P, Leiter LA, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Peters RJ, Held C, Chazova I, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Sanchez-Vallejo G, McKelvie R, Pogue J, Jung H, Gao P, Diaz R, Lonn E; HOPE-3 Investigators. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2021-31. doi: 10.1056/NEJMoa1600176. Epub 2016 Apr 2.
citation: Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3.
citation: Kataoka Y, St John J, Wolski K, Uno K, Puri R, Tuzcu EM, Nissen SE, Nicholls SJ. Atheroma progression in hyporesponders to statin therapy. Arterioscler Thromb Vasc Biol. 2015 Apr;35(4):990-5. doi: 10.1161/ATVBAHA.114.304477. Epub 2015 Feb 26.
citation: Berggren AM, Nyman EM, Lundquist I, Bjorck IM. Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats. Br J Nutr. 1996 Aug;76(2):287-94. doi: 10.1079/bjn19960032.
citation: Lu Y, Fan C, Li P, Lu Y, Chang X, Qi K. Short Chain Fatty Acids Prevent High-fat-diet-induced Obesity in Mice by Regulating G Protein-coupled Receptors and Gut Microbiota. Sci Rep. 2016 Nov 28;6:37589. doi: 10.1038/srep37589.
citation: Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, MacDougall K, Preston T, Tedford C, Finlayson GS, Blundell JE, Bell JD, Thomas EL, Mt-Isa S, Ashby D, Gibson GR, Kolida S, Dhillo WS, Bloom SR, Morley W, Clegg S, Frost G. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015 Nov;64(11):1744-54. doi: 10.1136/gutjnl-2014-307913. Epub 2014 Dec 10.
citation: Haghikia A, Zimmermann F, Schumann P, Jasina A, Roessler J, Schmidt D, Heinze P, Kaisler J, Nageswaran V, Aigner A, Ceglarek U, Cineus R, Hegazy AN, van der Vorst EPC, Doring Y, Strauch CM, Nemet I, Tremaroli V, Dwibedi C, Krankel N, Leistner DM, Heimesaat MM, Bereswill S, Rauch G, Seeland U, Soehnlein O, Muller DN, Gold R, Backhed F, Hazen SL, Haghikia A, Landmesser U. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism. Eur Heart J. 2022 Feb 10;43(6):518-533. doi: 10.1093/eurheartj/ehab644.