Nutritional Ketosis as a Novel Therapeutic Strategy to Stabilize Chronic Aortic Dissection in Marfan Syndrome
| Registry | NCT07495267 |
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| Status | Not yet recruiting |
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| Phase | Not applicable |
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| Study type | Interventional; na, single group, masking: none, other |
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| Enrollment | 15 (Estimated) |
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| Sponsor | Washington University School of Medicine (Other) |
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| Conditions | Marfan Syndrome, Aortic Dissection |
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| Interventions | Ketogenic diet (Other) |
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| Dates | start 2026-03-13 (estimated), primary completion 2028-03-01 (estimated), completion 2028-03-01 (estimated), first posted 2026-03-27, last updated 2026-03-27 |
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Related Papers Related Patents Related Grants Related Experts
All trials for Marfan Syndrome All trials for Aortic Dissection All trials of Ketogenic diet
-Summary
In this pilot clinical trial, the investigators will test whether a carefully supervised ketogenic diet can safely help people with Marfan syndrome who already have a chronic or residual aortic dissection. Fifteen participants will work with a study coordinator and dietitian to learn how to follow the diet and will have regular guidance and check-ins. The participants will measure their blood ketone levels at home with a simple finger-stick device and relay their readings to the research team. Every three months, blood samples will also be collected to confirm the body's level of ketosis.
Participants will continue their usual heart and blood-pressure medicines and regular visits with their doctors. Standard of care computed tomography (CT) scans of the aorta will be performed at the start of the study and then again at 6 and 12 months to see if the aorta changes in size.
The main goal is to see how many patients can avoid needing aortic surgery within one year, compared with what is normally expected from past studies. The investigators will also track how well patients follow the diet, how their aorta changes, and whether inflammation in their blood decreases.
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| Prospective Cohort | Experimental | Other: Ketogenic diet | Participants will initiate a supervised ketogenic diet formulated to provide approximately 70-75% of calories from fat, 20% from protein, and less than 10% from carbohydrates, consistent with protocols successfully used in therapeutic epilepsy trials but adapted for adult cardiovascular patients.
They will measure their blood ketone levels at home with a simple finger-stick device and relay their readings to the research team. Every three months, blood samples will also be collected to confirm the body's level of ketosis.
Participants will continue their usual heart and blood-pressure medicines and regular visits with their doctors. Standard of care computed tomography (CT) scans of the aorta will be performed at the start of the study and then again at 6 and 12 months to see if the aorta changes in size. |
- Ketogenic diet (Other): Participants will continue ketogenic diet for 12 months.
+Outcome measures
Primary outcomes
- Freedom from aortic intervention [12 months]: Freedom from aortic intervention at 12 months compared with historical controls.
Secondary outcomes
- Aortic dissection and inflammatory markers [12 months]: Observation of changes related to aortic dissection and inflammatory markers
- Number of Participants who Maintained Diet Adherence measured by Ketone Monitor [From day 1 to 12 months]: In order to measure adherence, participants will use a handheld ketone meter (Keto-Mojo) to measure β-hydroxybutyrate levels three times per week via saliva as well as finger-stick blood testing.
+Eligibility
Sex: All, ages: 18 Years to 50 Years
Inclusion Criteria:
1. Adults between 18 and 50 years old.
2. Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document.
3. Genetically or clinically confirmed Marfan syndrome
4. Chronic descending thoracic aortic dissection present for at least three months
5. Maximal descending thoracic aortic diameter must measure between 4.0 and 5.0 cm at baseline on contrast-enhanced computed tomography angiography (CTA)
6. Have been clinically stable and consistent antihypertensive regimen for at least four weeks
Exclusion Criteria:
1. Acute or rapidly enlarging dissection (>0.5 cm increase over the preceding three months)
2. Prior descending thoracic aortic repair or endograft placement
3. Advanced renal or hepatic dysfunction
4. Poorly controlled diabetes requiring insulin
5. Active malignancy, pregnancy, or other metabolic or nutritional disorders that would contraindicate ketogenic therapy
6. Body mass index below 18 kg/m²
7. Inability to comply with dietary restrictions or follow-up imaging
8. Current enrollment in another interventional study, which in the opinion of the principal investigator, may confound study results.
9. Patients who, in the opinion of the principal investigator, are not suitable candidates for study participation.
+Publications
- Kaul N, Duan J, Cui D, Erlichster M, Chen Z, Anderson D, Chan J, Scheffer IE, Skafidas E, Liao J, Kwan P. Serial correlation between saliva and blood beta-hydroxybutyrate levels in children commencing the ketogenic diet for epilepsy. Epilepsia. 2025 Sep;66(9):3282-3292. doi: 10.1111/epi.18465. Epub 2025 May 24. PMID 40411493
- Huang J, Yeung AM, Bergenstal RM, Castorino K, Cengiz E, Dhatariya K, Niu I, Sherr JL, Umpierrez GE, Klonoff DC. Update on Measuring Ketones. J Diabetes Sci Technol. 2024 May;18(3):714-726. doi: 10.1177/19322968231152236. Epub 2023 Feb 16. PMID 36794812
- Neves GS, Lunardi MS, Lin K, Rieger DK, Ribeiro LC, Moreira JD. Ketogenic diet, seizure control, and cardiometabolic risk in adult patients with pharmacoresistant epilepsy: a review. Nutr Rev. 2021 Jul 7;79(8):931-944. doi: 10.1093/nutrit/nuaa112. PMID 33230563
- Roehl K, Sewak SL. Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy. J Acad Nutr Diet. 2017 Aug;117(8):1279-1292. doi: 10.1016/j.jand.2017.06.006. PMID 28754198
- Campello Jorge CA, Marway PS, Tjahjadi NS, Knauer HA, Patel HJ, Hofmann Bowman M, Eagle K, Burris NS. Growth Rate Assessed by Vascular Deformation Mapping Predicts Type B Aortic Dissection in Marfan Syndrome. J Am Heart Assoc. 2025 Mar 18;14(6):e039179. doi: 10.1161/JAHA.124.039179. Epub 2025 Feb 26. PMID 40008501
- Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85. doi: 10.1136/jmg.2009.072785. PMID 20591885
- Wagner AH, Zaradzki M, Arif R, Remes A, Muller OJ, Kallenbach K. Marfan syndrome: A therapeutic challenge for long-term care. Biochem Pharmacol. 2019 Jun;164:53-63. doi: 10.1016/j.bcp.2019.03.034. Epub 2019 Mar 27. PMID 30926475
- Wheeler JB, Ikonomidis JS, Jones JA. Connective Tissue Disorders and Cardiovascular Complications: The Indomitable Role of Transforming Growth Factor-beta Signaling. Adv Exp Med Biol. 2021;1348:161-184. doi: 10.1007/978-3-030-80614-9_7. PMID 34807419
- Huang K, Wang Y, Siu KL, Zhang Y, Cai H. Targeting feed-forward signaling of TGFbeta/NOX4/DHFR/eNOS uncoupling/TGFbeta axis with anti-TGFbeta and folic acid attenuates formation of aortic aneurysms: Novel mechanisms and therapeutics. Redox Biol. 2021 Jan;38:101757. doi: 10.1016/j.redox.2020.101757. Epub 2020 Oct 13. PMID 33126053
- Zhu H, Bi D, Zhang Y, Kong C, Du J, Wu X, Wei Q, Qin H. Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal Transduct Target Ther. 2022 Jan 17;7(1):11. doi: 10.1038/s41392-021-00831-w. PMID 35034957
- Patikorn C, Saidoung P, Pham T, Phisalprapa P, Lee YY, Varady KA, Veettil SK, Chaiyakunapruk N. Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials. BMC Med. 2023 May 25;21(1):196. doi: 10.1186/s12916-023-02874-y. PMID 37231411
- Chamma L, Chamma N, Mattar L, Slaybe M, Haidar S, Rizk R. Beyond epilepsy management: A narrative review of the health effects of ketogenic diets. Nutrition. 2025 Sep;137:112804. doi: 10.1016/j.nut.2025.112804. Epub 2025 Apr 16. PMID 40403346
- Augustin K, Khabbush A, Williams S, Eaton S, Orford M, Cross JH, Heales SJR, Walker MC, Williams RSB. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. Lancet Neurol. 2018 Jan;17(1):84-93. doi: 10.1016/S1474-4422(17)30408-8. Epub 2017 Dec 16. PMID 29263011
- Weng X, Pan L, Ma X, Luo W, Su H, Pei Z, Dong Z, Liu L, Yang J, Gao P, Sun A. Ketogenic diet and beta-hydroxybutyrate inhibit HDAC1 to preserve vascular smooth muscle cell function in thoracic aortic aneurysm. J Adv Res. 2026 Feb;80:475-486. doi: 10.1016/j.jare.2025.05.035. Epub 2025 May 19. PMID 40398746
- Sastriques-Dunlop S, Elizondo-Benedetto S, Arif B, Meade R, Zaghloul MS, English SJ, Liu Y, Zayed MA. Ketosis Prevents Abdominal Aortic Aneurysm Rupture Through CCR2 Downregulation and Enhanced MMP Balance. bioRxiv [Preprint]. 2023 Feb 22:2023.02.21.529460. doi: 10.1101/2023.02.21.529460. PMID 36865192
- Zaghloul MS, Elizondo-Benedetto S, Zayed MA. Impact of ketogenic diet on cardiovascular disease. Nutr Rev. 2024 Dec 1;82(12):1835-1844. doi: 10.1093/nutrit/nuad152. PMID 38109885
- Sastriques-Dunlop S, Elizondo-Benedetto S, Arif B, Meade R, Zaghloul MS, Luehmann H, Heo GS, English SJ, Liu Y, Zayed MA. Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance. Sci Rep. 2024 Jan 16;14(1):1438. doi: 10.1038/s41598-024-51996-7. PMID 38228786
- Milewicz DM, Ramirez F. Therapies for Thoracic Aortic Aneurysms and Acute Aortic Dissections. Arterioscler Thromb Vasc Biol. 2019 Feb;39(2):126-136. doi: 10.1161/ATVBAHA.118.310956. PMID 30651002
- Tinkle BT, Lacro RV, Burke LW; COUNCIL ON GENETICS. Health Supervision for Children and Adolescents With Marfan Syndrome. Pediatrics. 2023 Apr 1;151(4):e2023061450. doi: 10.1542/peds.2023-061450. PMID 36938616
- Pitcher A, Spata E, Emberson J, Davies K, Halls H, Holland L, Wilson K, Reith C, Child AH, Clayton T, Dodd M, Flather M, Jin XY, Sandor G, Groenink M, Mulder B, De Backer J, Evangelista A, Forteza A, Teixido-Tura G, Boileau C, Jondeau G, Milleron O, Lacro RV, Sleeper LA, Chiu HH, Wu MH, Neubauer S, Watkins H, Dietz H, Baigent C; Marfan Treatment Trialists' Collaboration. Angiotensin receptor blockers and beta blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. Lancet. 2022 Sep 10;400(10355):822-831. doi: 10.1016/S0140-6736(22)01534-3. Epub 2022 Aug 29. PMID 36049495
- Asano K, Cantalupo A, Sedes L, Ramirez F. Pathophysiology and Therapeutics of Thoracic Aortic Aneurysm in Marfan Syndrome. Biomolecules. 2022 Jan 14;12(1):128. doi: 10.3390/biom12010128. PMID 35053276
- Milewicz DM, Braverman AC, De Backer J, Morris SA, Boileau C, Maumenee IH, Jondeau G, Evangelista A, Pyeritz RE. Marfan syndrome. Nat Rev Dis Primers. 2021 Sep 2;7(1):64. doi: 10.1038/s41572-021-00298-7. PMID 34475413
- Hofmann Bowman MA, Eagle KA, Milewicz DM. Update on Clinical Trials of Losartan With and Without beta-Blockers to Block Aneurysm Growth in Patients With Marfan Syndrome: A Review. JAMA Cardiol. 2019 Jul 1;4(7):702-707. doi: 10.1001/jamacardio.2019.1176. PMID 31066871
- Fleischmann D, Afifi RO, Casanegra AI, Elefteriades JA, Gleason TG, Hanneman K, Roselli EE, Willemink MJ, Fischbein MP; American Heart Association Council on Cardiovascular Radiology and Intervention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; and Council on Cardiovascular Surgery and Anesthesia. Imaging and Surveillance of Chronic Aortic Dissection: A Scientific Statement From the American Heart Association. Circ Cardiovasc Imaging. 2022 Mar;15(3):e000075. doi: 10.1161/HCI.0000000000000075. Epub 2022 Feb 17. PMID 35172599
- MacGillivray TE, Gleason TG, Patel HJ, Aldea GS, Bavaria JE, Beaver TM, Chen EP, Czerny M, Estrera AL, Firestone S, Fischbein MP, Hughes GC, Hui DS, Kissoon K, Lawton JS, Pacini D, Reece TB, Roselli EE, Stulak J. The Society of Thoracic Surgeons/American Association for Thoracic Surgery clinical practice guidelines on the management of type B aortic dissection. J Thorac Cardiovasc Surg. 2022 Apr;163(4):1231-1249. doi: 10.1016/j.jtcvs.2021.11.091. Epub 2022 Jan 25. No abstract available. PMID 35090765
- Isselbacher EM, Preventza O, Hamilton Black J 3rd, Augoustides JG, Beck AW, Bolen MA, Braverman AC, Bray BE, Brown-Zimmerman MM, Chen EP, Collins TJ, DeAnda A Jr, Fanola CL, Girardi LN, Hicks CW, Hui DS, Schuyler Jones W, Kalahasti V, Kim KM, Milewicz DM, Oderich GS, Ogbechie L, Promes SB, Gyang Ross E, Schermerhorn ML, Singleton Times S, Tseng EE, Wang GJ, Woo YJ; Peer Review Committee Members. 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2022 Dec 13;146(24):e334-e482. doi: 10.1161/CIR.0000000000001106. Epub 2022 Nov 2. PMID 36322642
- Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010 Apr 6;121(13):e266-369. doi: 10.1161/CIR.0b013e3181d4739e. Epub 2010 Mar 16. No abstract available. PMID 20233780
+Study documents