Nutritional Ketosis: a Novel Metabolic Strategy to Treat Lymphedema Patients?

NCT03991897 | Recruiting

• 2 other identifiers: S617672018-002968-10
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Lymphedema is a debilitating disorder that severely impairs the quality of life of the patients and requires life-long attention. Treatment for lymphatic dysfunction remains largely symptomatic, without real cure. According to the International Society of Lymphology, lymphedema has to be treated with Decongestive Lymphatic Therapy. Research in the lab of Angiogenesis and Vascular Metabolism (PCA lab) reported in mice that metabolism of endothelial cells controls vessel sprouting. Experiments showed that a ketogenic diet (KD) reduced the edema of the mice tail and enhanced the lymphatic transport. Based on these proof-of-concept data, the investigators plan to test this innovative concept to ameliorate lymph vessel dysfunction in lymphedema patients. Randomisation will be performed between a ketogenic diet and an isocaloric diet with and without ketone ester supplementation.

Conditions

Lymphedema; Ketogenic Dieting; Ketone Ester Supplement

Keywords

ketosis; lymphedema; dermal backflow

Outcome Measures

Primary Outcomes (2)

• Change in lymphatic transport

  Measured with lymphoscintigraphy

  Up to 12 weeks

• Change in lymphatic transport

  Measured by lymphofluoroscopy

  up to 12 weeks

Secondary Outcomes (7)

• Change in edema volume

  12 weeks

• Change in edema volume

  12 weeks

• Changed quality of life

  12 weeks

• Lymphatic function at 6 months

  6 months

• Change in edema volume at 6 months

  up to 6 months

Other Outcomes (1)

• Cost-effectiveness

  up to 6 months

Study Arms (3)

Ketogenic diet

EXPERIMENTAL

the intervention will consist of 3 phases: a two week run-in period, 12 weeks strict KD and 6 months Modified Atkins Diet. During the run-in period, patients will become familiar with their diet and, in particular, they will learn which foods are allowed and which are not. Ketogenic ratio wil build up to 3:1 - 4:1, ensuring protein needs.

Dietary Supplement: Ketogenic diet

Isocaloric diet

ACTIVE COMPARATOR

During the run-in period, the dietician will discuss the diet and maintenance of an isocaloric diet with the patients. As such, the diet of the control group will not change from their normal dietary pattern. In the latter case, the patient will be asked to change the diet to a normal Belgian diet, according to Flemisch dietary guidelines.

Dietary Supplement: Isocaloric diet

Ketone ester supplementation

EXPERIMENTAL

Arm Description: the intervention will consist of 3 phases: a two week run-in period, 12 weeks strict of Ketone ester supplementation and 6 months of the follow-up with a healthy diet. Ke supplements will be ingested 3 times a day separately from a meal in fixed doses of 25g. If blood β-OHB levels are substantially below 3mmol/L, a weight-based dosing of the KEs (up to 0.5g/kg bodyweight), rather than a fixed dosing strategy, will be utilized.

Dietary Supplement: Ketone ester supplementation

Interventions

Isocaloric diet DIETARY_SUPPLEMENT

Patients will follow an isocaloric diet

Isocaloric diet

Ketone ester supplementation DIETARY_SUPPLEMENT

25g of a ketone monoester, ingested 3 times a day for a period of 12 weeks. Ingestion is separated from a meal and interspersed by at least 4 hours to ensure maximal available ketone bodies circulating in the blood.

Ketone ester supplementation

Ketogenic diet DIETARY_SUPPLEMENT

Multivit and Metarelax. This multivitamin and Magnesium supplement will provide necessary vitamins and decrease ketone-flu sympotms, repsectively.

Ketogenic diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years;
• unilateral lymphedema of the arm lymph node dissection
• lymphedema onset less than a year before the therapy starts
• lymphedema defined as \>3% volume difference between both arms
• lymphedema stage 1, stage 2a or stage 2b
• absence of pregnancy at the time of enrollment and willingness to use adequate contraceptive measures until the end of the study;
• oral and written approval of the informed consent presented at the time of the consultation by the physicians;
• understanding Dutch

You may not qualify if:

• \<18 years;
• presence of active cancer
• pregnancy or active breastfeeding;
• impossibility to participate for the entire study period;
• mentally or physically unable to participate to the study;
• presence of gastrointestinal intolerance or other serious illness (e.g. renal failure, hepatic dysfunction, heart failure, neurological impairment);
• presence of diabetes or other metabolic disease;
• contra-indication for the use of indocyanine green (ICG): allergy to ICG or iodine, hyperthyroidism.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Related Publications (2)

• Lodewijckx I, Matthys C, Verheijen J, Verscuren R, Devoogdt N, Van der Schueren B, Goffin K, Fourneau I, Thomis S. Potential therapeutic effect of a ketogenic diet for the treatment of lymphoedema: Results of an exploratory study. J Hum Nutr Diet. 2024 Aug;37(4):885-891. doi: 10.1111/jhn.13330. Epub 2024 Jun 4.

  PMID: 38837503 RESULT

• Garcia-Caballero M, Zecchin A, Souffreau J, Truong AK, Teuwen LA, Vermaelen W, Martin-Perez R, de Zeeuw P, Bouche A, Vinckier S, Cornelissen I, Eelen G, Ghesquiere B, Mazzone M, Dewerchin M, Carmeliet P. Role and therapeutic potential of dietary ketone bodies in lymph vessel growth. Nat Metab. 2019 Jul;1(7):666-675. doi: 10.1038/s42255-019-0087-y. Epub 2019 Jul 12.

  PMID: 32694649 RESULT

MeSH Terms

Conditions

Lymphedema; Ketosis

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Nicolas Timmermans, Msc

  KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Thomis, MD

CONTACT

003216346948; sarah.thomis@uzleuven.be

Christoph Matthys, PhD

CONTACT

003216342655; christophe.matthys@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After baseline assessment, patients will be randomized in one of the treatment groups. Randomization is performed according to 'www.randomization.com'. This free generator randomizes each subject to a single treatment by using the method of randomly permuted blocks. Assessments are performed by a person blinded to the treatment allocation groups. Randomization will be stratified for baseline lymphedema volume (3-9.9%, 10.0-19.9% and ≥20%), and gender (females or males). The staff members who perform the measurements are blinded for the allocation.

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: June 19, 2019
• Study Start: October 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)