Risks of Ramadan Fasting in Patients With Primary Adrenal Insufficiency Treated With Prednisolone.

Hopital La Rabta

Status

Not yet enrolling

Conditions

Dehydration

Ramadan Fasting

Hypoglycemia Non-Diabetic

Continuous Glucose Monitoring

Primary Adrenal Insufficiency

Prednisolone

Treatments

Other: Ramadan fasting

Study type

Interventional

Funder types

Other

Identifiers

NCT07367425

HLaRabta26

Details and patient eligibility

About

In primary adrenal insufficiency (PAI), there is a risk of hypoglycemia and dehydration. These risks seem to be increased during intermittent fasting. A previous study in patients with PAI treated with hydrocortisone at a dose of 20 mg/day showed that the prevalence of hypoglycemia was as high outside (63%) as during Ramadan fasting (71%), and that there was no risk of dehydration. We propose to evaluate the risk of complications during and outside of Ramadan fasting through a prospective study with subjects taken as their own controls, in 35 patients with PAI treated with prednisolone at a dose of 5 mg/day. Patients will undergo an interview, physical examination, blood sampling, and continuous glucose monitoring (CGM) during two weeks of fasting and two weeks of non-fasting.

Full description

The risk of hypoglycemia in adrenal insufficiency is known but poorly studied. It is due to cortisol deficiency. Only a few publications have addressed this topic. The risk of hypoglycemia is thought to be increased during acute decompensation, following treatment discontinuation, and during fasting or delayed eating. Thus, this risk is thought to be increased during intermittent fasting, such as the Ramadan fast. A previous study conducted in the endocrinology department of La Rabta Hospital, involving 30 subjects with corticotropic insufficiency who underwent 24-hour continuous glucose monitoring (CGM), identified three cases of hypoglycemia during intermittent fasting and no hypoglycemia outside of fasting periods. A more recent study showed that the prevalence of hypoglycemia, assessed by a seven day-CGM, was 63% outside of fasting and 71% during Ramadan fasting in subjects with PAI substituted with hydrocortisone at the usual dose of 20mg/day.

The most commonly used glucocorticoid replacement therapy is based on hydrocortisone or cortisone. Prednisolone is also indicated, particularly in cases difficult to control with hydrocortisone. The usual dose is 5 mg/day. It has been suggested to replace hydrocortisone with prednisolone to reduce the risk of complications during Ramadan fasting. However, this has never been demonstrated. A previous study showed that the prevalence of complications, quality of life, and point-in-time capillary blood glucose measurements were not different with hydrocortisone or prednisolone.

On the other hand, the risk of dehydration and hypotension seems to be low in patients treated with hydrocortisone.

General objective:

To evaluate the risks of intermittent fasting in subjects with PAI treated with prednisolone 5 mg/day.

Specific objectives:

To evaluate the frequency of hypoglycemia in subjects with PAI treated with prednisolone 5 mg/day during and outside of Ramadan fasting.
To evaluate the frequency of dehydration in subjects with PAI treated with prednisolone 5 mg/day during and outside of Ramadan fasting.
To study the factors associated with hypoglycemia and dehydration.

Study type: prospective, interventional, with the subject serving as their own control.

Visit 1: 4 weeks before Ramadan

Verification of inclusion and exclusion criteria.
Explanation of the study objectives and procedures.
Obtaining informed consent from the patient.
Switching from hydrocortisone to prednisolone 5 mg/day. Fludrocortisone will be continued, and the dose will be adjusted if necessary.

Visit 2: 14 days before Ramadan, patients treated with prednisolone for 14 days.

This visit will include an interview, a physical examination, placement of a CGM system, and a fasting blood sample.

Interview:

Demographic data: age, sex
Data related to PAI: duration, etiology, replacement therapy. History of fasting and its duration (number of days fasted, occurrence of complications).
Quality of life questionnaire (AddiQoL) and sleep quality questionnaire (PSQI). Physical examination: weight, height, waist circumference, blood pressure (lying and standing), heart rate, presence of hyperpigmentation, signs of dehydration.

The CGM device, consisting of a subcutaneous sensor (2.5 mm flexible catheter) and a transmitter (single-use), will be inserted. This device measures and records interstitial glucose every three minutes for 14 days.

The CGM application will be downloaded to the patient's or a parent's smartphone for data collection and transmission.

Issuance of monitoring sheets. During the 14 days of CGM, patients will be required to complete a monitoring sheet including medication intake, wake-up and bedtimes, physical activity, and any adverse events (fatigue, signs of hypoglycemia, signs of hypotension, or other symptoms). Patients will be contacted by one of the investigators by telephone to ensure adherence to the protocol and to monitor for any potential complications.
Laboratory tests: urea, electrolytes.

Visit 3: During Ramadan (the first 14 days). This visit will include an interview, a physical examination, placement of the CGM device, and a fasting blood sample, following the same procedure as Visit 2.

The patient will receive dietary and lifestyle advice regarding fasting.
Monitoring forms will be provided. During this study period, patients will also be required to complete the same monitoring form. Patients will also be contacted by one of the investigators by telephone to verify adherence to the protocol and to monitor for any potential complications.

The criteria for breaking the fast are:

Occurrence of discomfort during fasting, hypoglycemia on MCG, elevated urea, or hyperkalemia.

Visit 4: After Ramadan, patients should submit their monitoring records.

Diagnostic criteria:

First-degree hypoglycemia is defined as an interstitial glucose level measured during continuous glucose monitoring (CGM) < 0.70 g/L for more than 15 minutes, and second-degree hypoglycemia as an interstitial glucose level < 0.55 g/L for more than 15 minutes.
Dehydration is defined by the onset of arterial hypotension (BP < 90/60 mmHg or orthostatic hypotension) or an elevation of plasma urea.

Statistical analysis:

The frequencies of hypoglycemia and dehydration will be calculated and compared between the fasting and non-fasting periods. Mean blood glucose levels per period (suhoor-5 a.m.; 5 a.m.-10 a.m.; more than 10 a.m. after suhoor) will also be calculated and compared between the fasting and non-fasting periods. Univariate and potentially multivariate analyses will be conducted to determine the factors associated with hypoglycemia and dehydration.

Enrollment

35 estimated patients

Sex

All

Ages

20 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

subjects with primary adrenal insufficiency known for at least one year, treated with a glucocorticoid and a mineralocorticoid, who wish to fast during Ramadan 2026.

Exclusion criteria

presence of diabetes, renal, hepatic, cardiac, or respiratory insufficiency; use of hypoglycemic agents (sulfonylureas), diuretics, use of any glucocorticoid other than the prescribed replacement therapy; poor disease control (asthenia, malaise, hyperpigmentation, discontinuation of treatment, etc.); pregnancy; breastfeeding; menstruation.