## Protocol Section
### Identification Module
**NCT ID:** NCT06418074

**Acronym:** (KETO-HT)

**Brief Title:** Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity

**Official Title:** Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity in Patients With Essential Hypertension

#### Organization Study ID Info
**ID:** TZL-1-2024
#### Organization
**Class:** OTHER
**Full Name:** Gødstrup Hospital
### Status Module
#### Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-06
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Gødstrup Hospital

#### Responsible Party

**Investigator Affiliation:** Gødstrup Hospital

**Investigator Full Name:** Trine Lyksholm

**Investigator Title:** Principal investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This is a randomized, placebo-controlled, double-blinded crossover design. Nineteen patients with essential hypertension will be randomized to receive either ketone bodies (KE4) or placebo delivered by KetoneAid. After a period of 5-days treatment, effect variables will be measured (experiment day 1). After a washout period of 14 days, the subjects are crossed over to a similar treatment period with the other treatment. The study is terminated by measuring effect variables after the second treatment period (experiment day 2).

**Detailed Description:** Background: Renewed interest in ketone bodies has emerged, partly driven by the recent success of selective sodium glucose co transporter 2 (SGLT-2) inhibition in preventing cardiovascular deaths in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Effects of ketosis are of importance in order to understand the beneficial effects of SGLT-2 inhibitors and to account for the full therapeutic potential of this treatment.

Hypothesis: Ketosis decreases 24 hour systolic blood pressure and increases renal blood flow and glomerular filtration rate (GFR).

Methods: It is a randomized, placebo-controlled double-blinded cross over study. Nineteen patients with essential hypertension will be randomized to receive either ketone bodies (KE4) or for 5 days. After a wash out period of at least 14 days, the subjects are crossed over to receive the other treatment. After each treatment period effect variables will be measured including Technetium(Tc)99m - Diethylenetriamine pentaacetate (DTPA) clearance and water based positron emission tomography computed tomography (PET/CT)

Perspectives: The study has the potential to provide information regarding the therapeutic potential of treatment with ketone bodies and understanding of conditions characterized by ketosis, such as SGLT2-inhibitor treatment.

### Conditions Module

**Conditions:**

- Ketosis

- Essential Hypertension

**Keywords:**

- Natriuresis

- Kidney circulation

- Kidney physiology

- Glomerular Filtration Rate

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 19

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** For five days each subject will receive beta-hydroxybutyrate (KE4), then crossed over to receive placebo drink for 5 days.

**Intervention Names:**

- Dietary Supplement: Beta-hydroxybutyrate

- Other: Placebo

**Label:** KE4, then Placebo drink

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** For five days each subject will receive a placebo drink three times daily, then subjects are crossed over to receive beta-hydroxybutyrate (KE4).

**Intervention Names:**

- Dietary Supplement: Beta-hydroxybutyrate

- Other: Placebo

**Label:** Placebo drink, then KE4

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- KE4, then Placebo drink

- Placebo drink, then KE4

**Description:** Each subject will receive Beta-hydroxybutyrate 300mg/kg x 3 for five days. After the treatment period effect variables will be examined.

**Name:** Beta-hydroxybutyrate

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- KE4, then Placebo drink

- Placebo drink, then KE4

**Description:** Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.

**Name:** Placebo

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Change in systolic 24-hour blood pressure

**Measure:** 24-hour systolic blood pressure

**Time Frame:** Measured after each treatment period (each treatment period is 6 days)

#### Secondary Outcomes

**Description:** Change in RBF determined by water based PET/CT scans

**Measure:** Renal Blood Flow (RBF)

**Time Frame:** Measured after each treatment period (each treatment period is 6 days)

**Description:** Change in GFR measured by Tc99m-DTPA clearance

**Measure:** GFR

**Time Frame:** Measured after each treatment period (each treatment period is 6 days)

**Description:** Change in plasma levels of aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin

**Measure:** Vasoactive hormones

**Time Frame:** Measured after each treatment period (each treatment period is 6 days)

**Description:** Change ind p-beta-hydroxybutyrate concentration

**Measure:** P-Beta-hydroxybutyrate

**Time Frame:** Measured after each treatment period (each treatment period is 6 days)

**Description:** Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC)

**Measure:** Plasma concentration of renal tubular transport proteins

**Time Frame:** Measured after each treatment period (each treatment period is 6 days)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Essential hypertension (treatment with maximum 2 antihypertensive drugs)
* eGFR \> 60ml/min
* BMI \< 35 kg/m2
* Urine Albumin Creatinin Ratio (UACR) \< 300mg/g
* Safe contraception if women in childbearing age

Exclusion Criteria:

* Diabetes type 1 or 2
* Heart Failure
* Pregnancy or breast feeding
* Liver disease
* Malignant disease
* Recent acute myocardial infarction (AMI), apoplexia/transient ischemic attack (TIA) (within 12 months of inclusion)
* Daily use of prescription drugs (expect for contraceptives)
* Alcohol or drug abuse
* Periodic fasting
* Routinely intake of ketogenic diet
* Treatment with immunosuppressants or SGLT2-inhibitors

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** trizur@rm.dk

**Name:** Trine Z Lykshom, MD

**Phone:** 78432534

**Phone Ext:** 0045

**Role:** CONTACT

**Contact 2:**

**Name:** Jesper N Bech, MD, prof

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** The University Clinic for Nephrology and Hypertenion, Regional Hospital Godstrup

**Name:** Trine Z Lyksholm, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000000138

- Term: Acidosis

- ID: D000000137

- Term: Acid-Base Imbalance

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: Hypertension

- ID: M1470

- Name: Essential Hypertension

- Relevance: HIGH

- As Found: Essential Hypertension

- ID: M10687

- Name: Ketosis

- Relevance: HIGH

- As Found: Ketosis

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M3499

- Name: Acidosis

- Relevance: LOW

- As Found: Unknown

- ID: M3498

- Name: Acid-Base Imbalance

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006973

- Term: Hypertension

- ID: D000075222

- Term: Essential Hypertension

- ID: D000007662

- Term: Ketosis

### Misc Info Module

- Version Holder: 2024-05-31
