Ketogenic diet and ketone ester to reduce arm lymphedema

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

This trial will test whether a ketogenic diet, with or without ketone ester supplements, can reduce swelling in adults with recent unilateral arm lymphedema after lymph node removal.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 81 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitaire Ziekenhuizen KU Leuven (Academic / other)
• Locations: 1 site (Leuven)
• Trial ID: NCT03991897 on ClinicalTrials.gov

What this trial studies

Participants with early unilateral arm lymphedema will be randomized to a ketogenic diet or an isocaloric control diet, and some groups will receive ketone ester supplementation, to induce nutritional ketosis and compare outcomes. The study will measure limb volume differences, dermal backflow and markers of lymphatic transport to determine changes in edema and function. Eligible participants are adults with stage 1 to 2b lymphedema that started within one year after lymph node dissection and who can give informed consent in Dutch. The trial is motivated by mouse proof-of-concept data showing reduced edema and improved lymphatic transport under ketogenic conditions.

Who should consider this trial

Good fit: Adults over 18 with unilateral arm lymphedema onset within the past year, defined as >3% volume difference and stage 1–2b after lymph node dissection, who can consent and understand Dutch.

Not a fit: Patients with active cancer, pregnancy or breastfeeding, edema from other causes or later-stage disease than specified, major organ failure, significant gastrointestinal intolerance, or inability to adhere to the diet are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, inducing nutritional ketosis could reduce limb swelling, improve lymphatic transport, and enhance quality of life for people with early post-surgical arm lymphedema.

How similar studies have performed: Preclinical mouse studies from the investigators' lab showed reduced edema and improved lymphatic transport with a ketogenic diet, but human data on ketosis for lymphedema are currently limited.

Eligibility criteria

Inclusion Criteria:

* \>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

Exclusion Criteria:

* \<18 years;
* edema of the limb with different etiology or later stage/onset as specified in the inclusion criteria;
* 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.

Where this trial is running

Leuven

• UZ Leuven — Leuven, Belgium (Recruiting)

Study contacts

• Principal investigator: Nicolas Timmermans, Msc — KU Leuven
• Study coordinator: Sarah Thomis, MD

Conditions Lymphedema; Ketogenic Dieting; Ketone Ester Supplement; ketosis; lymphedema; dermal backflow